Cocaine abuse by methadone-maintained patients threatens to undermine the success of methadone programs by sustaining a drug-abusing lifestyle as well as contributing to the spread of HIV. The search for a pharmacotherapeutic agent for the treatment of cocaine has met with limited success. The most promising results emerge when specific agents, such as desipramine, are matched appropriately to specific patient characteristics, such as depression or antisocial personality disorder. For some patients, abstinence from cocaine may also require the addition of intensive psychosocial treatments that target the considerable problems faced by inner-city opioid-addicted individuals. This article discusses ways in which future research could be directed toward investigating the interaction between psychosocial services and pharmacologic treatments, while at the same time developing and testing hypotheses concerning appropriate patient-treatment matching variables.