In 2009, the United Nations estimated that 33.2 million people worldwide were living with human immunodeficiency virus type 1 (HIV-1) infection and that 2.6 million people had been newly infected.1 The need for effective HIV-1 prevention has never been greater. In this review, we address recent critical advances in our understanding of HIV-1 transmission and acute HIV-1 infection. Fourth-generation HIV-1 testing, now available worldwide,2,3 will allow the diagnosis of infection in many patients and may lead to new treatments and opportunities for prevention.