With the advent of the human immunodeficiency virus (HIV) protease inhibitors and the non-nucleoside reverse transcriptase inhibitors, the importance of drug-drug interactions with antiretroviral agents is becoming increasingly recognized. Every clinician involved in the care of HIV-infected persons should have a broad knowledge of these drug-drug interactions and their underlying mechanisms. This paper will review currently known clinically relevant interactions with antiretroviral agents reported thus far. Alternative strategies will be proposed where possible, in order to improve patient safety and the therapeutic efficacy of the antiretroviral agents. It must be emphasized, however, that in many cases these proposals are not backed up by authoritative clinical consensus panels and that clinical experience with many of these combinations is limited.