This chapter reviews pharmacological options that may improve the impaired wakefulness associated with shift work disorder (SWD) and available data regarding the use of stimulant therapy. It begins with a brief discussion of shift work and SWD. Night shift workers are at a greater risk for workplace accidents than day shift workers. Research into the negative physical and mental effects of shift work is accumulating, and available evidence indicates that shift work is associated with greater risk of psychiatric problems, cardiovascular disorders, cancer, and accidents, and it represents a serious occupational health problem. A variety of countermeasures have been proposed and studied for the treatment of sleepiness and daytime sleep disturbances associated with shift work. These countermeasures range from basic nonpharmacological and behavioral strategies for improving sleep quality and quantity to pharmacological interventions for improving alertness during the work period or for improving sleep during the sleep period.