A useful clinical framework for decision making in antiretroviral treatment is to consider treatment options and goals at 4 decision points: initial therapy, early treatment failure, late treatment failure with high CD4+ cell count, and late treatment failure with low CD4+ cell count. Basic principles appropriate to these decision points are discussed. For initial treatment, the goal is to suppress viral replication for as long as possible. In early failure, the aim is to achieve resuppression of viral replication. For late treatment failure in patients with high CD4+ cell counts with limited treatment options, a reasonable approach is to be cautious in making treatment changes, since sustained incomplete suppression is not associated with immunologic collapse. In patients with late treatment failure and lower CD4+ cell counts, a reasonable strategy is to maintain some form of antiretroviral therapy until new drug classes become available. These basic approaches are reviewed in this article, with findings reported at the recent 10th Conference on Retroviruses and Opportunistic Infections discussed in light of this strategic framework. This article summarizes a presentation given by Diane V. Havlir, MD, at the March 2003 International AIDS Society-USA course in Los Angeles.