Cocaine addiction is a persistent and insidious public health problem (Pomara et al, 2012). Despite evidence for sustained prevalence, clinical harm, and demand for treatment, the Food and Drug Administration (FDA) has yet to approve any pharmacotherapy for its treatment. ‘Agonist' medications such as amphetamine maintenance have emerged as one intriguing but controversial class of candidates, and this Circumspectives Article presents pros and cons of agonist medications for treatment of cocaine-use disorder. Evidence in favor of agonist medications will be presented by Dr Steve Negus. Dr Negus has contributed for more than 20 years to research on medications development for drug-abuse treatment, and he published early preclinical data supporting efficacy of amphetamine maintenance to reduce cocaine self-administration. Regulatory challenges to the use of agonist medications will be presented by Dr Jack Henningfield. Dr Henningfield also has decades of experience in preclinical and clinical evaluation of both abuse potential of novel drugs and utility of candidate treatments. He was involved in the research and regulatory processes that led to FDA approval of various nicotine agonist therapies and of buprenorphine as an analgesic and agonist therapy.