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The use and misuse of a broad spectrum of psychoactive substances, including heroin and cocaine, is of growing concern in many African countries. Approximately one-third of global HIV and AIDS cases are reported from Africa, but injecting drug use has not yet been documented as a causative factor. The drug supply control strategy has recorded only limited success in Africa, and the currently adopted demand reduction programs are beset with many problems. In this paper we review possible constraining and facilitating factors in the adoption of harm reduction approaches in high risk sub-Saharan African countries. We conclude that appropriate needs assessments are urgently required to establish the extent of problem drug use and of injecting. This exercise may identify clinical and psychosocial problems that could benefit from an intervention approach based on a combination of the principles of harm reduction and demand reduction.