It has recently been estimated that persons with the acquired immunodeficiency syndrome (AIDS) receive on average 5.6 prescription medications throughout their disease course, and this number may be as high as 9 [1,2]. With the development and testing of new antiretroviral agents and drugs for opportunistic infections associated with human immunodeficiency virus (HIV) disease, the issue of polypharmacy and multiple drug interactions will become increasingly complex. Since antiretroviral therapy and treatment or prophylaxis of opportunistic infections is lifelong, the nature of these interactions requires delineation to provide an optimal pharmacologic strategy for the use of these agents in combination. This article will address antiretroviral drug interactions from a pharmacokinetic and pharmacodynamic perspective. A background on the clinical pharmacology of antiretroviral agents is provided as is a discussion of selected interations. © 1995.