Worldwide, the heterosexual route is the prevalent mode of HIV-1 transmission, and the female reproductive tract accounts for approximately 40% of all HIV-1 transmissions. HIV-1 infection in the female reproductive tract involves three major events: entry through the mucosal epithelium, productive infection in subepithelial mononuclear cells, and delivery to lymph nodes to initiate systemic infection. Here, we provide a focused review of the interaction between HIV-1 and mucosal epithelial cells, lymphocytes, macrophages, and dendritic cells in female genital mucosa. Increased understanding of these interactions could illuminate new approaches for interdicting HIV-1 heterosexual transmission. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.