Sleep, like breathing, is a biologic rhythm that is actively generated by the brain. Neuronal networks that have evolved to regulate naturally occurring sleep preferentially modulate traits that define states of sedation and anesthesia. Sleep is temporally organized into distinct stages that are characterized by a unique constellation of physiologic and behavioral traits. Sleep and anesthetic susceptibility are genetically modulated, heritable phenotypes. This review considers 40 yr of research regarding the cellular and molecular mechanisms contributing to arousal state control. Clinical and preclinical data have debunked and supplanted the primitive view that sleep need is a weakness. Sleep deprivation and restriction diminish vigilance, alter neuroendocrine control, and negatively impact immune function. There is overwhelming support for the view that decrements in vigilance can negatively impact performance. Advances in neuroscience provide a foundation for the sea change in public and legal perspectives that now regard a sleep-deprived individual as impaired.