The major US treatment guidelines recently recommended starting antiretroviral therapy (ART) later in the course of HIV infection due to an increasing awareness of the difficulties associated with these regimens. Most of the data to support this change come from observational cohort studies. When deciding to start ART, a number of patient-specific factors and other issues should be considered. Given the many choices for initial ART, one should individualize the choice, taking into account antiretroviral regimen potency, durability, side effects, toxicities, and convenience to ensure a sustained clinical benefit for the patient.