This chapter discusses the significant burden of disease from opioid use compared to other psychotropic substances, including the significant economic, social, and health impacts of opioid use. It describes harm reduction initiatives such as medication for opioid use disorders and needle and syringe programmes that have shown promise in lowering the rates of illicit opioid use, risky injection drug use, and other health-related outcomes, including blood-borne virus transmission and improvement in quality of life. This chapter explores the context contributing to opioid trafficking and use in Sub-Saharan Africa, the extent of the problem, the consequences of opioid use, and the barriers limiting the adoption, implementation, and expansion of harm reduction programmes. It then proposes strategies for policy and workforce development and offers recommendations for action.