Sequencing of antiretroviral agents is of interest because the majority of HIV-infected individuals in clinical practice experience virologic rebound after 1 to 2 years of therapy. Sequencing strategies are based on the observation that different mutational patterns arise after exposure to particular antiretroviral agents within the same class and on preliminary data suggesting that not all mutations impart the same degree of cross-resistance to other agents of the same class. The ultimate goal of sequencing is to maximize the number of effective antiretroviral combinations available. While convincing data on the efficacy of sequencing strategies from large, randomized clinical trials are lacking, early data suggest that some sequencing strategies may be of benefit.