To paraphrase David Parkes [1], insomnia can be called by different names just like Wordsworth’s [2] cuckoo (“O Cuckoo! Shall I call thee Bird, or but a wandering Voice?”) because insomnia is thought to be a symptom of many diseases (medical, psychiatric, and others). For an understanding of insomnia, one should begin by studying the inhabitants of the ancient world and the civilization of the Indus (India), Yangtze (China), the Euphrates (Middle East) [1], and Egypt gradually progressing through to modern industrialized and contemporary culture. The term insomnia is derived from Latin meaning literally a total lack of sleep. But from a practical standpoint it is the relative lack of sleep, non-restorative, or inadequate quality of sleep which is relevant. Insomnia is really “hyposomnia” meaning a decrease in duration or depth. Henry Cockeram while working on the dictionary of “hard English words” in the early 1620s [3] used the term insomnia synonymous with the word “watching” meaning want of power to sleep.

Frank in 1811 mentioned agrypnia (meaning insomnia) as one of the seven classes of sleep disturbance [17]. A search of the literature clearly shows that publications on the topic of insomnia dominated the field of sleep research since 1870. For a description of historical evolution of insomnia and its treatment in the nineteenth and early twentieth centuries, the readers are referred to Chap. 12 by Schulz and Salzarulo. Macfarlane [18] in 1890 wrote the definitive text of the nineteenth century defining insomnia as “loss of sleep.” It is interesting to note that Macfarlane considered insomnia as a symptom and not a disease, a view still hotly debated in this century.

Contemporary sleep medicine defines insomnia as an inability to fall asleep or maintain sleep associated with an impairment of daytime functioning. International classification of sleep disorders (ICSD-3) [19] classified insomnia into three categories. It can be associated with medical, psychiatric or psychological factors, environmental causes, or ingestion of medication. The term secondary insomnia used in the first National Institute of Health (NIH) consensus development conference in 1983 has been replaced by the term comorbid insomnia in the later NIH consensus conference in 2005 [20] as the cause-and-effect relationship has not been determined. The Diagnostic and Statistical Manual of the American Psychiatric Association (1994; DSM-IV) classified insomnia into primary insomnia and that related to medical or mental disease or to substance abuse or dependency. DSM-V (published in 2013) recommends the term “insomnia disorders” replacing “primary insomnia” and “insomnia associated with medical or mental diseases” [21]. According to the Center for Disease Control (CDC) of the USA, 70 million Americans suffer from chronic insomnia. The lack of a standard definition of insomnia hampered epidemiological studies and limited research on sleep quality. Depending on the definition, up to 30 % of the population in the Western countries may experience insomnia symptoms and insomnia may be persistent in 10 % [22]. Insomnia diagnosis is based on subjective reports (sleep questionnaires and sleep diaries) rather than objective data derived from polysomnographic (PSG) findings. In any case, there appears to be a remarkable discrepancy between PSG and subjective measures. Edinger et al. published research diagnostic criteria for insomnia [23]. Longitudinal studies of the general population in the Western countries suggested high prevalence with varying degrees of persistence with rates varying from 40 to 69 % and the incidence rates of 3.9 to 28.8 % [22]. In a longitudinal study (mean follow-up of 5.2 years) of Chinese adults, the researchers in Hong Kong led by Y. K. Wing found an incidence rate for insomnia symptoms and insomnia syndrome (additional daytime symptoms) of 5.9 %, whereas the persistence rate of insomnia syndrome was 42.7 and 28.2 % for insomnia symptoms [24].

Some major advances in insomnia research occurred in the last half of the twentieth and twenty-first century. Some examples of these include long-term consequences of chronic insomnia, relationship between insomniac and psychiatric disorders, new understanding about pathophysiology of insomnia, and advances in the treatment. First, one must understand that insomnia is a 24-h disease and is not just sleep deprivation. Sleep deprivation is endemic in our modern industrialized society. Average sleep duration in human has decreased by 1.5–2 h in the course of the last 55 years, which may be partly responsible for adverse metabolic and hormonal effects, and increasing incidence of obesity and type 2 diabetes mellitus in the society [25]. Function of sleep, however, remains a mystery but we have enough evidence to show that sleep plays an important role in homeostatic mechanism with restitution of sleep, thermoregulation, immune control, and tissue repair, as well as memory consolidation [26]. Even one night of sleep deprivation impairs hippocampal function resulting in inadequate memory processing [27]. Jenkins and Dallenbach’s experiment in 1924 [28] proved that memory retention was better after a night of sleep and this was later supported by behavioral and functional magnetic resonance imaging (fMRI) studies by Stickgold and Walker [29]. An early observation by Kripke et al. [30] in 1979 of increased risk of death from coronary arterial disease, cancer, and stroke in those who sleep less than 4 h (also those who sleep more than 10 h) was later confirmed [31], but remains controversial without resolving cause and effect and because of the confounding factor of medication ingestion. However, short-term consequences, such as excessive daytime sleepiness , mood disorder, irritability, impaired work efficiency and absenteeism, accidents at work and home, and falls in the elderly, and long-term (remains debatable) consequences, such as increased mortality and morbidity (e.g., obesity, type 2 diabetes mellitus, hypertension , and other adverse cardiovascular consequences, psychiatric disorders, and memory impairment, have been reported in patients with chronic insomnia [32]. Obstructive sleep apnea (OSA) is an additional comorbidity and up to 50 % of OSA patients may suffer from moderate to severe insomnia [33]. There is a clear bidirectional relationship between insomnia and depression [34]. In 1969, Winokur et al. [35] reported that 100 % of their sample of 1257 patients with depression had comorbid insomnia and these observations have been subsequently confirmed in many reports [34].

Significant advances have been made in the last decade of the twentieth and current century in our understanding of the pathophysiology of chronic insomnia. There are many models and theories proposed. Various models focused on primary insomnia rather than comorbid insomnias as the latter represent heterogeneous conditions. Richardson [36] proposed four physiological models: (1) disruption of the sleep homeostat; (2) disruption of the circadian clock; (3) disruption of intrinsic sleep–wake state mechanisms; and (4) disruption (hyperactivity) of extrinsic “override” systems (e.g., stress response mechanisms). A detailed discussion of these models is beyond the scope of this chapter but available data favor the involvement of dysfunctional extrinsic stress response systems. Physiological hyperarousal remains the contemporary theory inspired by studies undertaken earlier by Monroe [37], Kales [38], Adam [39], and coinvestigators, Bonnet and Arand [40] and continuing with Perlis [41], Vgontzas et al. [42], and other investigators [36]. Perlis [41, 43] and coinvestigators have provided a comprehensive review of the hyperarousal theory. The sustained hyperarousal throughout 24 h explains the persistence of chronic primary insomnia. The hyperarousal theory is based on the evidence of physiologic arousal with increased autonomic activity (e.g., elevated heart rate and body temperature), sympathetic arousal (measured by heart rate variability), activation of neuroendocrine (e.g., hypothalamo–pituitary–adrenal [HPA] and neuroimmunological axes), and heightened cortical arousal (e.g., increased beta and gamma frequency electroencephalography (EEG) activity at sleep onset and during non-REM (NREM) sleep with the higher high-to-low frequency ratio in the fast Fourier transformation (FFT) of the EEG signals, and altered brain metabolism as evidenced by the positron emission tomographic (PET) scan findings of heightened neural activation in brain areas subserving arousal and emotion during sleep in insomnias) [41, 43–46]. The increased production of cortisol and interleukin-6 in patients with chronic insomnia support the activation of the HPA and neuroimmunological axes [42]. The finding of a reduction in hippocampal volume [47] in insomnias and the experimental observations of impaired neurogenesis in the hippocampus following sleep loss in rats [48] support cognitive deficits and impaired memory consolidation in patients with chronic insomnia. Finally, using a sophisticated immunohistochemical method (Fos activation indicating neuronal activation), Cano et al. [49] produced a stress-induced insomnia model in rats to show simultaneous activation of both sleep-promoting and arousal-related brain regions similar to the observations in human insomniacs of simultaneous fatigue throughout the day and an inability to “de-arouse” on attempting to sleep.