The rapid increase in communication and transportation between Africa and other continents as well as the erosion of social fabric attended by poverty, ethnic conflicts, and civil wars has led to increased trafficking and consumption of illicit drugs. Cannabis dominates illicit trade and accounts for as much as 40% of global interdiction. Due to escalating seizures in recent years, the illicit trade in heroin and cocaine has become a concern that has quickly spread from West Africa to include Eastern and Southern Africa in the past 10 years. All regions of Africa are characterized by the use of cannabis, reflecting its entrenched status all over Africa. Most alarming though is the use of heroin, which is now being injected frequently and threatens to reverse the gain made in the prevention of HIV/AIDS. The prevalence of HIV infection and other blood-borne diseases among injection drug users is five to six times that among the general population, calling for urgent intervention among this group. Programs that aim to reduce the drug trafficking in Africa and needle syringe programs as well as medication-assisted treatment (MAT) of heroin dependence while still in their infancy in Africa show promise and need to be scaled up.