HCO₃^– plays critically important roles during virtually the entire process of reproduction in mammals, including spermatogenesis, sperm capacitation, fertilization, and development of early stage embryos. Therefore, the acid-base balance in the male and female reproductive tracts must be finely modulated. The fluid milieu in the epididymis is acidic, containing very low concentration of HCO₃^–. In this acidic low HCO₃^– environment, mature sperm are rendered quiescent in the epididymis. In contrast, the luminal fluid in the female uterus and oviduct is alkaline, with very high concentration of HCO₃^– that is essential for sperm to fulfill fertilization. HCO₃^– transporter of solute carrier 4 (SLC4) and SLC26 families represent the major carriers for HCO₃^– transport across the plasma membrane. These transporters play critical roles in intracellular pH regulation and transepithelial HCO₃^– transport. The physiological roles of these transporters in mammalian reproduction are of fundamental interest to investigators. Here we review recent progress in understanding the expression of HCO₃^– transporters in reproductive tract tissues as well as the physiological roles of these transporters in mammalian reproduction.