Poor adherence to antiretroviral treatment regimens has serious consequences for human immunodeficiency virus-infected patients, including failure to prevent viral replication and an increased risk of developing viral resistance. Recent data suggest that the level of medication adherence required for optimal treatment effectiveness is extremely high. Treatment adherence can be measured by use of a variety of methods, including patients' self-reports, pharmacy-based approaches, pill counts, and electronic monitoring. However, these measures of adherence have different strengths and weaknesses in regard to practical application and identifying deficient adherence. All patients receiving antiretroviral therapy require support to insure a high level of treatment adherence, but the evidence about effective interventions is limited. Emerging evidence suggests adherence interventions should employ a multidisciplinary effort involving health care providers, social support networks, family, and friends. Although such programs will require a substantial investment in terms of time and energy, the rewards associated with optimal treatment adherence are worth the effort.