Many clinicians who care for patients with HIV infection are dissatisfied with the existing recommendations on antiretroviral therapy. Current practice focuses on the early suppression of viremia, yet the outcome of that approach may not be in the best interest of individual patients or populations. The major goal of HIV therapy is to maintain the long-term health of the patient while avoiding drug-related toxicity and preserving viable future treatment options. Recent studies have challenged the principles on which recommendations for early, aggressive treatment were based. Key studies that lead to licensure of antiretroviral medications usually involve short-term results in treatment-naive patients; it is difficult to apply these results to long-term management of therapy-experienced patients. Early, aggressive therapy often prematurely exposes patients to risks for medication-related side effects and resistance. A more cautious, patient-focused, long-term approach to therapy would help foster studies of alternate strategies, such as delayed initiation of therapy, protease-sparing therapy, class-sparing therapy, planned drug interruptions, switches in therapy, and immune-based therapy. It is time for clinicians to rethink their approach to the treatment of HIV infection.