It is beyond the scope of the present article to review the literature on the pharmacologic reversal of sleep loss-related alertness and performance deficits, but some general trends warrant discussion. The extent to which stimulants reverse various sleep loss-induced effects has received much attention, particularly for simple psychomotor tasks and sleep propensity. In short, the currently available stimulants (or “wakefulness-promoting agents” in the case of modafinil), including caffeine, modafinil, dextroamphetamine, and methylphenidate, improve response speed and the ability to maintain wakefulness in a dose-dependent fashion and along a time course that is consistent with the half-lives of various compounds (eg, longer duration effects with dextroamphetamine and modafinil relative to caffeine). Stimulant effects on executive functions have been less well studied. The results of several studies10,55 have suggested that some functions are restored by some compounds but that no one compound restores all functions. The results from these studies are limited by a lack of dose-response information, the inclusion of only a subset of executive function tasks, and a lack of baseline (ie, non-sleep deprived) performance measures on tasks for which multiple versions do not exist (which is the case for many tasks of executive function). Also largely unstudied is the extent to which stimulants maintain efficacy when used long term to reverse chronic sleep restriction effects (whether due to chronic insufficient nighttime sleep or daytime sleep associated with night shift work) in otherwise healthy adults. The effects of stimulants on subsequent sleep generally vary as a function of their half-lives and the timing of sleep periods. Sleep is not overtly disrupted when initiated 20 h after the administration of a stimulant (eg, caffeine, modafinil, or d-amphetamine),55 but is disrupted if attempted within 3 h of caffeine administration56 or within 6.5 h after the administration of dextroamphetamine or modafinil.57 The roles of various neurotransmitter systems in sleep/wake periods continue to be explored and elucidated, and it is likely that better pharmacologic methods of managing sleep and wakefulness will be developed in the coming decades.