Although the practice of clinical neurology often appears as functioning as a separate and independent organ system, the nervous system does not operate in a vacuum. There are numerous relationships between the nervous system and other organ systems, some of which have been recently elucidated, that can lead to a multitude of neurologic manifestations of systemic disease. Indeed, there are several new neurologic problems that are now recognized as being secondary to primary pathology from other organ systems. This chapter surveys the common neurologic manifestations of systemic diseases that commonly occur in the older adult. The chapter will highlight the following organ systems: cardiac, pulmonary, gastrointestinal, endocrine, rheumatologic, immunologic/oncologic, and renal.