Several aspects of mammary gland biology make it a fascinating model for the study of normal development and disease. Glandular morphogenesis proceeds largely in two postnatal phases, during puberty and pregnancy, with terminal differentiation occurring only with lactation. Thus, for the majority of a woman’s reproductive life, the gland exists in a state that is immature, but poised to undergo rapid proliferative, morphological, and biochemical differentiation. The fact that mammary gland development and risk for cancer are both exquisitely sensitive to endogenous and exogenous factors, such as hormones and diet, likely reflects these unique temporal differentiation patterns. Further, evolutionarily, the mammary gland is a relative recent tissue to arise, and evidence suggests that developmental programs associated with other tissues such as immune, bone, liver and nerve have been ‘borrowed’ to fulfill the novel functions required of the normal gland. The result is the overlay of rich and diverse genetic programs that interact to yield biology that may be unique to the mammary gland, including gland plasticity, but also renders the gland susceptible to oncogenesis. Because the functional unit of the mammary gland is the epithelial cell plus its microenvironment, these aspects of mammary gland biology will be presented from a stromal-epithelial perspective. The intent is to provide a systems approach to mammary gland biology by highlighting cutting-edge research in these topic areas.