Electrical lighting and increasing capital intensiveness have helped undermine the importance that society previously placed on obtaining adequate sleep. Even modest amounts of daily sleep loss accumulate as “sleep debt.” Sleep debt manifests in a myriad of ways, the most common being an increasing tendency to fall asleep, increased risk of accidental injury, impaired mood, and reduced psychomotor performance. Sleep debt can have far reaching consequences, both to an individual in terms of increased cardiovascular risk and to society at large, because of sleepiness-related fatigue and errors. Sleep specialists need to further their understanding of the physiologic and behavioral consequences of total, partial, and selective sleep stage deprivation, because they affect many organ systems. Studies of selective sleep stage deprivation also provide insights into the function of sleep. Evaluating the effects of sleep deprivation must take into account the following factors: (1) the duration of prior sleep, (2) circadian time frame, (3) arousal influences, and (4) subject and test characteristics. Sleep deprivation has been extensively studied in the acute experimental setting. Under extreme conditions, sleep deprivation is associated with mortality in laboratory animals. In the natural human environment, the behavioral consequence of chronic sleep debt in shift work intolerance is well described. The link between electrophysiological sleep disturbance and pathogenesis of disease is less well understood in both acute and chronic states. Additional investigation into the relationship between sleep deprivation and disease mechanisms, such as impaired glucose tolerance, hormonal dysregulation, and cytokine imbalance, will enhance our comprehension of this link.