There are, at present, 22 compounds which have been formally approved (by the US Food and Drug Administration) for the treatment of HIV infections (AIDS). According to their point of intervention with the HIV replicative cycle, these compounds can be classified in 5 categories: (1) NRTIs (nucleoside reverse transcriptase inhibitors): azidothymidine, didanosine, zalcitabine, stavudine, lamivudine, abacavir and emtricitabine; (2) NtRTIs (nucleotide reverse transcriptase inhibitors): tenofovir, administered as its oral prodrug form TDF (tenofovir disoproxil fumarate); (3) NNRTIs (non-nucleoside reverse transcriptase inhibitors): nevirapine, delavirdine and efavirenz; (4) PIs (HIV protease inhibitors): saquinavir, ritonavir, indinavir, nelfinavir, amprenavir, lopinavir, atazanavir, fosamprenavir, tipranavir and darunavir; and (5) FIs (fusion inhibitors): enfuvirtide. Starting from the drugs which are currently available for the treatment of AIDS, numerous combinations could be envisaged. Drug combinations are, in principle, aimed at obtaining synergism between the compounds (reasonably expected if they act by different mechanisms), while reducing the likelihood for drug resistance development. Such anti-HIV drug combination regimes were initiated about 10 years ago and have been generally referred to as HAART (for highly active antiretroviral therapy). While HAART originally consisted of a pill burden of twenty (or more) pills per day, this has been gradually diminished over the past few years, and, since July 2006, a all-in-one pill (Atripla) has become available, which contains three anti-HIV drugs (tenofovir disoproxil fumarate, emtricitabine and efavirenz) to be taken as a single pill only once daily. Given the information that has been acquired on the therapeutic use (efficacy, safety) of tenofovir disoproxil fumarate over the past five years, it would now seem mandatory to further consider the prophylactic use of TDF [and its combination with emtricitabine (Truvada) and/or Atripla], as a single daily pill to prevent HIV infection.