Emerging evidence suggests that early events in human immunodeficiency virus type 1 (HIV-1) infection may play a critical role in determining disease progression. Although there is limited evidence on which to base medical decisions, the diagnosis and treatment of acute HIV-1 infection may have virologic, immunologic, and clinical benefits. In addition, rapid diagnosis of infection may prevent unknowing transmission of HIV-1 during a period of high-level viremia. We review the basic principles of primary HIV-1 infection, clinical and diagnostic markers of acute seroconversion, approaches to management, and new therapeutic strategies.