Pharmacotherapy remains a relatively underused strategy for the treatment of patients with psychoactive substance-use disorders. This is partly because of a widely held view among the public and the substance-abuse treatment community that substance-use disorders are non-medical and should be treated through nonpharmacologic means. Furthermore, the pharmaceutical industry has been slow in developing medications for the treatment of patients with these disorders because of skepticism over the potential profitability of such medications. These factors have limited research activity in this area, with much of the impetus for study of these medications coming from the National Institute on Drug Abuse and the National Institute on Alcohol Abuse and Alcoholism, where the substantial public health implications of medications development for substance-use disorders have been recognized. Despite limitations, considerable advances in medication development for patients with substance-use disorders have occurred in recent years, and more can be expected in the near future. This is most evident in the treatment of patients with nicotine and opioid dependence, for whom several pharmacologic options exist. Recently renewed interest in the pharmacologic treatment of patients with alcohol dependence is likely to advance that therapeutic area substantially with time. Ongoing efforts should focus on identifying new compounds, systematically assessing them for activity in specific substance-use disorders, and educating the public and the treatment community about the substantial benefits that can accrue from medication development for patients with substance-use disorders.