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Prescription stimulants, including methylphenidate (e.g., Ritalin) and amphetamine compounds (e.g., dextroamphetamine; Adderall), have been approved by the U.S. Food and Drug Administration for the treatment of attention-deficit/hyperactivity disorder (ADHD) and are classified by the United States Drug Enforcement Administration as Schedule II medications because of their high potential for abuse and dependence (Drug Enforcement Administration, U.S. Department of Justice, 2015). Despite the potential health and judicial consequences, misuse of prescription stimulants, typically defined as taking stimulants without a valid prescription, or use of stimulants other than as prescribed, has become a serious problem in the United States and abroad, especially on college campuses. The purpose of the present article is to review historical information concerning prescription stimulants and to summarize the literature with respect to misuse among adults, particularly college students, including risk factors, mediators and moderators, and motivations for prescription stimulant misuse. In addition, evidence is presented concerning the question of whether prescription stimulants truly enhance cognitive functioning in individuals with and without ADHD, and the ethical and professional implications of these findings are explored. Lastly, recommendations for addressing prescription stimulant misuse and suggestions for future research are advanced.