Administration of antiretroviral agents is a cornerstone of therapy for HIV infection and combination therapy is a key to the decreased HIV-associated morbidity and mortality seen since the late 1990s. Appropriate dosing of these agents has become increasingly complex because of the use of combinations of drugs referred to as highly active antiretroviral therapy. These regimens are often associated with an increased likelihood for drug-drug interactions and overlapping toxicity profiles. To dose these drugs most appropriately, the pharmacodynamic relationships between these drugs must be understood and then applied in general clinical practice to evaluate outcome.