Cocaine was considered incapable of producing dependence in 1980 but was recently proclaimed the drug of greatest national health concern. Recent clinical and preclinical investigations demonstrate that cocaine produces unique abuse and withdrawal patterns that differ from those of other major abused drugs and suggest that long-term cocaine abuse produces neurophysiological alterations in specific systems in the central nervous system that regulate the capacity to experience pleasure. It will be necessary to develop clinically pertinent research models before these findings can be considered definitive, but these evolving ideas have already led to applications of promising experimental treatments for cocaine abuse.