Amphetamine, first discovered in 1887, and the subsequently developed stimulants have been used in clinical psychiatry with varying results. Beyond their use for attention-deficit/hyperactivity disorder (ADHD), they have been used for symptomatic relief based on their effects on mood and hedonic drive. Research into the use of stimulants as adjunctive agents in the treatment of specific symptoms and syndromes has been increasing. Evaluation of new medications, such as modafinil and armodafinil, which are classified as wakefulness-promoting agents, has further heightened interest in a possible therapeutic role for such agents in treatment of neurobehavioral disorders. Various common adjunctive psychotherapeutic uses for stimulants, such as depression, have not been well researched, while other indications, such as narcolepsy, are backed by considerable clinical data. Nonetheless, much more data are needed on the safety and efficacy of traditional psychostimulants as well as the newer agents in the treatment of psychiatric disorders. In this chapter, we review the pharmacology of these medications and their indications (Tables 43–1 and 43–2).