Measurement of adherence may be important in determining why patients fail antiretroviral therapy. Although patient self-report is by far the most frequently used means of assessing adherence, it overestimates adherence. However, patients who state they are nonadherent almost always are. The pill identification test is a recently described tool that may be useful in clinical practice. The best methods of adherence measurement are pill counts and electronic monitoring. Pill counts suffer from inability to record the time of consumption of therapy. Electronic monitoring enables timing of pill consumption and is the closest to a gold standard for measuring adherence. However, this is only the case if patients are carefully instructed in how to use the device, e.g., not to remove extra doses from their pill bottle. A composite adherence score has been developed that uses electronic monitoring, pill counts, and patient self-report. The authors believe that careful measurement of adherence is essential in the assessment of a patient failing to respond to antiretroviral therapy.