A variety of medications are used in treating patients infected with the human immunodeficiency virus (HIV). These medications are used to control viremia and to prevent and treat opportunistic infections. An individual is often required to take numerous drugs at the same time and thus clinicians are confronted with potential drug interactions, some of which are significant. Three different groups of anti-HIV drugs are used to treat patients. These groups include nucleoside reverse transcription inhibitors, non-nucleoside reverse transcription inhibitors, and protease inhibitors. This article reviews the most relevant drug interactions that occur during the treatment of HIV-infected patients with traditional and also alternative drugs. The role of therapeutic drug monitoring in the routine management of HIV-infected patients is discussed.