Zidovudine remains one of the most commonly prescribed agents for patients with HIV infection. A variety of drug interactions have been reported that may alter blood levels of zidovudine and concomitantly administered drugs or may involve overlapping toxicities. Several concomitant medications have been shown to alter the plasma concentrations of zidovudine, although most of these interactions are not thought to be clinically important. Use of agents that share the bone marrow-suppressive properties of zidovudine require additional monitoring for the development of hematologic toxicity. An understanding of potential mechanisms and important zidovudine-related interactions will aid in the optimal care of the HIV-infected patient.