Over the past 15 years, more than 20 antiretroviral drugs have been approved for the treatment of human immunodeficiency virus-1 (HIV-1) infection. The combined use of these drugs (the so called “highly active antiretroviral therapy” [HAART]) has substantially improved the clinical management of HIV-1 infection in terms of delaying disease progression, prolonging survival, and improving quality of life. Nevertheless, new therapeutic strategies in the management of HIV infected, treated individuals must be constantly considered to minimize the emergence of drug resistance and to maximize the opportunity to set up a long-term successful antiretroviral treatment. Decisions about the most appropriate strategy for anti-HIV treatment must be individualized.