The past 2 years have witnessed stunning benefits of antiretroviral therapy. Dramatic delays in HIV progression, improved survival, and decreased hospitalization for HIV-infected patients have created a renewed sense of optimism [1–2]. For many, HIV disease has been transformed into a manageable chronic disease. However, complete enthusiasm for these recent successes has been dampened by biological, clinical, social, and economic realities that limit both access to and success of antiretroviral therapies. High HIV replication and mutation rates, varying potency of regimens, stage of HIV disease, and previous antiretroviral therapy all influence therapeutic success and failure. In addition, it has become increasingly clear that differing levels of adherence to therapy explain much of the magnitude and durability of the therapeutic response. For example, clinical trials of antiretroviral therapies have shown reductions in HIV-1 RNA copies to levels less than 500 copies/mm3 in up to 80% to 85% of patients , but results in clinical sites may be as low as 50% . In both settings, adherence predicts which patients achieve nondetectable viral levels [4–6].