The range of antiretroviral medications both in current use and in development is large, including five classes that do not overlap in their development of resistance. They are used in combinations generally including three or four drugs, and it is not feasible to test all possible combinations. Guidelines are available, however, thanks to the efforts of industry and academia to determine best treatment choices and alternatives. Considerations in the initial choice of antiretrovirals include likelihood of complete viral suppression, likelihood of adherence, development of side effects, and saving potent therapy for future therapy. Resistance testing, either phenotypic or genotypic or both, is useful in selecting subsequent regimens.