The advent of combination antiretroviral therapy for the treatment of human immunodeficiency virus (HIV) infection has dramatically changed the prognosis and quality of life of HIV-infected adults and children. To date, there are 21 antiretroviral agents available with only 11 agents being approved for the use in young children less than 6 years of age. The currently available antiretroviral agents belong to four different classes; nucleoside/nucleotide reverse transcriptase inhibitors (NRTI, NtRTI), non-nucleoside reverse transcriptase inhibitors (NNRTI), protease inhibitors (PI), and a new class of fusion inhibitors (FI). It is recommended that the treatment regimen should be a combination of at least 3 drugs from different drug classes as this has been shown to slow disease progression, improve survival, and result in better virologic and immunologic responses. Treatment with antiretroviral agents is frequently complicated by the issues of adherence, tolerability, long term toxicity and drug resistance. Many efforts have been made to develop new antiretroviral agents with greater potency, higher tolerability profiles and better convenience. Some new agents are also effective against drug-resistant strains of HIV. Since 2001, there were 7 new antiretroviral agents and 2 fixed-dose multidrug formulations being approved for the treatment of HIV infection, most are approved only for use in adults. In this article, we will review new antiretroviral agents including emtricitabine, tenofovir disoproxil fumarate, atazanavir, fosamprenavir, tipranavir and enfuvirtide. Pediatric information on these drugs will be provided when available.