Growing concerns over endocrine disrupting chemicals (EDCs) and their effects on human fetal development and adult health have promoted research into the underlying molecular mechanisms of endocrine disruption. Gene targeting technology has allowed insight into the genetic pathways governing reproductive tract development and how exposure to EDCs during a critical developmental window can alter reproductive tract development, potentially forming the basis for adult diseases. This review primarily uses diethylstilbestrol (DES) as a model agent for EDCs and discusses the recent progress elucidating how DES and other EDCs affect murine female reproductive tract development and cancer at the molecular level.