Managing fatigue in complex operational settings requires attention to multiple factors, including hours of service, scheduling, education and training, counter-measures, technology, and research. Alertness-management strategies can be used to promote safety, performance, and productivity in operational settings. These strategies can involve both preventive (used prior to duty/shift) and operational (used during duty/shift) approaches. Studies have demonstrated the effectiveness of naps to improve subsequent performance and alertness. Strategic naps can be used effectively to promote performance and alertness in operational settings. Two potential negative effects of naps, sleep inertia and effects on subsequent sleep periods, are discussed. Sleep inertia can involve sleepiness and decreased performance immediately upon awakening from a nap. It should be a consideration prior to implementing nap strategies in work environments. A study of planned rest periods in long-haul flight operations demonstrated the effectiveness of in-flight naps to promote performance and alertness during subsequent critical phases of flight (descent and landing). Empirical evaluation of alertness-management strategies during regular operations will be critical to their implementation. Combining strategies may be the most effective approach to managing fatigue engendered by 24-h operational demands. Other considerations prior to implementing alertness-management strategies in operational environments are discussed.