There are at present exactly 25 compounds that have been formally approved for the treatment of retrovirus (that is HIV) infections: seven nucleoside reverse transcriptase inhibitors (NRTIs), one nucleotide reverse transcriptase inhibitor (NtRTI), four non-nucleoside reverse transcriptase inhibitors (NNRTIs), 10 protease inhibitors (PIs), one coreceptor inhibitor (CRI), one fusion inhibitor (FI) and one integrase inhibitor (INI). Other compounds expected to be approved for the treatment of HIV infections in the near future are the NNRTI rilpivirine, the CRI vicriviroc and the INI elvitegravir. To obtain synergistic activity, enable lower dosage levels, thus minimizing toxic side effects, and particularly to reduce the risk of drug resistance development, common wisdom dictates that the HIV inhibitors should be used in drug combination regimens. Although, given the number of compounds available, the drug combinations that could be concocted are uncountable, only one triple-drug combination has so far been formulated as single pill to be taken orally once daily, namely Atripla containing the NtRTI tenofovir disoproxil fumarate, the NRTI emtricitabine and the NNRTI efavirenz. Here, we document these approved compounds along with other HIV-active compounds and, for the first time, compounds whose principal activity is against hepatitis B virus. The logic of this new division being the enzymatic similarity between the reverse transcriptase of HIV and hepatitis B virus; the strategies for the development of antiviral agents to combat them have much in common.