The therapies now approved for HIV-infection inhibit one of two viral-specific enzymes, reversetranscriptase or protease. Combining this drugs into regimes based on at least three individual drugs--so-called HAART--has resulted in a remarkable reduction in HIV-associated morbidity and mortality. Despite these therapeutic advances, many patients are either intolerant of available agents or develop virologic failure. Problems of adherence, drug-resistance, latent reservoirs and drug-induced toxic effects that compromise effective viral control point to need for new strategies (e.g. structured treatment interruptions--STIs) and new classes of anti-HIV drugs with different modes of action (e.g. blocking HIV entry into human cells or fusion process). The use of adjunctive immune-based therapy such as IL-2 may permit more extensive immune restoration.