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.