Individuals with recent human immunodeficiency virus type 1 (HIV-1) acquisition are likely to be a major source for other new infections because they have a high level of plasma virus, and the circulating virions possess unique properties that are highly suited for transmission. The acute infection period, however, presents a unique "window of opportunity," because there are a limited number of genetic variants. Studies aim to elucidate the nature of the transmitted viruses and understand the mechanisms that inhibit the majority of variants present in the chronically infected partner from establishing a productive infection in the naive host. Greater understanding of these issues may open promising new ways to effectively block HIV-1 transmission.