Taking antiretroviral medications as directed is essential to reducing the plasma viral load. By controlling HIV replication, antiretroviral combination therapy enables the host's immune system to fortify itself and ward off opportunistic pathogens. However, adhering to antiretroviral regimens that include at least 3 different drugs taken once, twice, or 3 times a day is a constant challenge for patients with HIV disease. Care providers need to be aware of the challenges and obstacles faced by their patients on antiretroviral regimens, and efforts to maximize adherence must begin even before the patient has the first prescriptions filled.