Antiretroviral medications have the potential to transform HIV infection from a fatal to a chronic disease. One of the significant barriers to clinical success is medication nonadherence. Measuring adherence in clinical trials is increasingly important because inadequate adherence may explain some of the variation in clinical response in antiretroviral clinical trials. Additionally, to quantitate the success of interventions that improve adherence, accurate measures need to be utilized. This article summarizes commonly used adherence measures in HIV clinical trials and observational studies such as patient self-report, pill counts, plasma levels, and electronic monitoring. The merits and shortcomings of each measure are discussed.