A vast amount of knowledge has accumulated since the discovery of the immunodeficiency diseases caused by human immunodeficiency virus-1 (HIV-1) in the early 1980s. An expert panel of HIV researchers and clinicians produced the first set of treatment guidelines in 1997. Since then, these guidelines have been updated based on available clinical information and supplemented by expert opinion when scientific data were incomplete. The latest version of the HIV treatment guidelines are summarized here, with attention focused on the rationale for treatment of asymptomatic as well as symptomatic individuals, including when and what to start as a first regimen of highly active antiretroviral therapy (HAART). Components of initial and follow-up evaluations are detailed, with attention given to available HIV viral load tests and their use. Because adherence to HAART is critical to immune recovery and stabilization, data on predictors of both good and poor medication compliance, as well as strategies to maximize medication adherence are presented. Lastly, recommendations for the use of HIV genotypic and phenotypic resistance testing in antiretroviral naive patients are presented.