This chapter reviews the neurophysiology of normal human sleep, including the electrophysiological and neuroendocrine characteristics of the rapid eye movement (REM)/non-rapid eye movement (NREM) sleep stages. REM sleep, or stage R, usually follows a NREM sleep episode and consists of tonic and phasic components. It describes the electrophysiological assessment of sleep disorders with polysomnography (PSG). The chapter also discusses the organization of sleep (sleep architecture) in young healthy adults, and reports the effects of age, psychiatric disorders, and psychoactive medications on sleep architecture. Sleep architecture is fairly consistent in healthy adults, but changes significantly across the life-span, in psychiatric patients, or in subjects taking psychotropic medications. The chapter presents several neuroimaging techniques, including functional magnetic resonance imaging (fMRI), positron emission tomography (PET), and high-density electroencephalography (hd-EEG), which have been increasingly utilized in sleep research to explore the neuroanatomy of normal sleep and the effects of sleep deprivation on cognitive functions.