This review addresses potential new treatments for stimulant drugs of abuse, especially cocaine. Clinical trials of vaccines against cocaine and nicotine have been completed with the generally encouraging result that subjects showing high titers of antidrug antibody experience a reduction in drug reward, which may aid in cessation. New vaccine technologies, including gene transfer of highly optimized monoclonal antibodies, are likely to improve such outcomes further. In the special case of cocaine abuse, a metabolic enzyme is emerging as an alternative or added therapeutic intervention, which would also involve gene transfer. Such approaches still require extensive studies of safety and efficacy, but they may eventually contribute to a robust form of in vivo drug interception that greatly reduces the risks of addiction relapse.