Herbal medicines are widely used by HIV patients. Several herbal medicines have been shown to interact with antiretroviral drugs, which might lead to drug failure. We have aimed to provide an overview of the modulating effects of Western and African herbal medicines on antiretroviral drug-metabolizing and transporting enzymes, focusing on potential herb-antiretroviral drug interactions. Echinacea, garlic, ginkgo, milk thistle, and St. John's wort have the potential to cause significant interactions. In vitro and in vivo animal studies also indicated other herbs with a potential for interactions; however, most evidence is based on in vitro studies. Further pharmacokinetic studies to unveil potential Western and especially African herb-antiretroviral drug interactions are urgently required, and the clinical significance of these interactions should be assessed.