This chapter focuses on the extent to which modafinil sustains/restores various aspects of cognitive performance during sleep deprivation in normal healthy adults. The earliest published studies of modafinil's effects in humans were conducted by Saletu and colleagues, and involved non-sleep-deprived young adult and elderly volunteers. The first published study of modafinil's dose-response effects on cognitive performance during sleep loss was performed at the Defense Research and Development Canada (DRDC) laboratory. The focus of an increasing number of studies is the effect of sleep loss on tasks of executive functioning. Executive functions encompass a wide range of mental abilities including critical reasoning, planning, flexible thinking, and effective judgment. Deficits in one or more of these abilities due to sleep loss and circadian factors are thought to be the underlying cause of mishaps such as Three Mile Island.