Earlier initiation of antiretroviral therapy (ART) for human immunodeficiency virus (HIV)-1 infection is associated with reduced HIV-related morbidity and mortality, improved immune recovery, and reduced risk of HIV-1 transmission. Consequently, international guidelines now recommend ART for all HIV-1-infected adults, regardless of CD4 cell count. The shift in guidance has led to concern regarding long-term ART toxicity, and new strategies to limit ART exposure have been proposed. In this review, we will discuss current recommendations for ART and future trends in management including mono- and dual-therapy, new ART formulations, and novel antiretroviral agents.