Recent studies employing molecular, cellular, and whole organism approaches have identified the epidermal growth factor receptor (EGFR) and its ligands as key players in female reproductive functions. Gene expression studies demonstrated that the members of this family are expressed in a timely and spatially coordinated manner in different reproductive tissues. Manipulation of the EGFR system in rodent models by pharmacological or surgical means as well as elimination or overexpression of specific components of the EGFR system in genetically modified mice resulted in aberrant reproductive phenotypes, highlighting the physiological relevance of these molecules. This article summarizes the experimental evidence derived from rodent models, leading to our current understanding of the roles of the EGFR system in key steps of reproduction, such as ovulation, fertilization, embryo implantation, and the attainment of sexual maturity.