The use of herbal supplements and medicines is increasing rapidly as most people consider them to be of natural origin and therefore safe. Many herbal medications are used to treat diseases but while they are often efficacious, their safety has not sufficiently considered by physicians or users. One particular safety concern is the risk of interactions with drugs, which often lead to toxicity or loss of therapeutic efficacy. A significant number of patients combine herbal remedies with prescription medications and there is growing evidence for interactions of drugs with herbal remedies or single compound originating from plants. Current antiretroviral treatment has allowed human immunodeficiency virus (HIV) infection to become a chronic manageable condition with many HIV patients living longer. Among this HIV+ community, the use of natural health products and other forms of complementary and alternative medicines is increasing. As million of patients with HIV are put on treatment with the highly active antiretroviral therapy (HAART), drug interactions have become a major concern for healthcare providers. The use of HAART as a combination of three or four drugs creates the potential for antiretroviral drug interactions, and this is complicated by the addition of other drugs for treatment of other ailments such as comorbid chronic conditions and/or opportunistic infections. In this review, we have aimed to provide an overview of the effects of herbal medicines on antiretroviral drug-metabolizing and transporting enzymes, focusing on potential herb–antiretroviral drug interactions, as well as interactions at the pharmacodynamic level.