Sub-Saharan Africa is the epicenter of the HIV pandemic and HIV-infected people are more susceptible to inflammatory dermatoses, infections, and drug eruptions. Many of the drugs used for HIV-associated opportunistic infections are associated with a higher incidence of drug-related toxicities and drug interactions. This article discusses the epidemiology, pharmacogenetics, and clinical features of idiosyncratic drug reactions in HIV-infected Africans. Special considerations in this population, including immune reconstitution inflammatory syndrome, multiple drug hypersensitivity syndrome, drug reactions in pregnancy, drug rechallenge in lichenoid drug eruptions, and anxiety/depression after cutaneous adverse drug reactions, are also briefly discussed.