The recent availability of new antiretroviral agents for the treatment of human immunodeficiency virus (HIV) infection has increased treatment options and has improved the durability, tolerability, and long-term efficacy of antiretroviral therapy, even among patients with extensive treatment experience and high levels of drug resistance. This expansion of therapeutic options has led to a revision of current treatment guidelines, which now state that the goal of antiretroviral therapy in all patients is suppression of the plasma HIV RNA level to <50 copies/mL. Successful management of infection for treatment-experienced patients with the new agents requires an understanding of their pharmacology and resistance patterns and the appropriate use of laboratory testing to optimize regimen selection. This review discusses the use of recently approved antiretroviral agents in the management of HIV infection in treatment-experienced patients.