An optimal fluid microenvironment in the female reproductive tract is considered to be crucial for successful reproductive events. Fluid absorption and secretion across the reproductive tract epithelia largely depends on electrolyte transport through the apically and basolaterally located ion channels, working together with an array of other transporters. This review will discuss the role of epithelial sodium channel (ENaC) and the cystic fibrosis transmembrane conductance regulator (CFTR) in regulating the fluid volume and composition of the reproductive tract and their importance in various reproductive events such as sperm capacitation and implantation. Disturbance of the fluid microenvironment due to defects or abnormal regulation of these ion channels as causes for a number of pathological conditions, such as ovarian hyperstimulation syndromes, hydrosalpinx and infertility, is also discussed.