Best practice for the clinical management of acute human immunodeficiency virus (HIV) infection remains unknown. Although some data suggest possible immunologic, virologic, or clinical benefit of early treatment, other studies show no difference in these outcomes over time, after early treatment is discontinued. The literature on acute HIV infection is predominantly small nonrandomized studies, which further limits interpretation. As a result, the physician is left to grapple with these uncertainties while making clinical decisions for patients with acute HIV infection. Here we review the literature, focusing on the potential advantages and disadvantages of treating acute HIV infection outlined in treatment guidelines, and summarize the presentations on clinical management of acute HIV infection from the 2009 Acute HIV Infection Meeting in Boston, Massachusetts.