Fatigue has been identified as an important operational problem in both military and civilian aviation (Caldwell, 1997; Rosekind et al., 2000). Requirements for extended duty periods, inconsistent work/rest schedules, multiple-time-zone operations, and night flights combine to potentially degrade performance and alertness in the cockpit. Duty-time limitations traditionally have been relied upon to manage aircrew fatigue; but problems persist as evidenced by the fact that significant fatigue-related mishaps continue to occur. Because of this, it may be worthwhile to consider the limited use of alternative strategies such as stimulants. The data from five placebo-controlled studies (four with dextroamphetamine and one with modafinil) were combined to examine the overall efficacy of stimulants for preserving flight performance, physiological alertness, and subjective vigilance in sleep deprived pilots. Statistically-significant (p<.05) drug main effects and drug-by-time interactions revealed that both compounds maintained flight performance across six maneuvers, attenuated deprivation-related increases in slow-wave electroencephalogram (EEG) activity, and preserved subjective ratings of psychological vigor throughout 34-39 hours of continuous wakefulness, whereas substantial difficulties were observed under placebo. Furthermore, the drug- related effects were remarkably consistent across all of the five studies that were examined. Dextroamphetamine and modafinil are effective for sustaining aviator alertness and performance (although, some potentially dose-related adverse effects were observed with modafinil). While it may be ill-advised to rely upon the long-term use of these or other pharmacological strategies as the sole remedy for fatigue in aviation, stimulants can be counted upon to temporarily mitigate the deleterious effects of fatigue during operations in which no other countermeasures are feasible.