Although mammary stem cells were first identified almost two decades ago, recent progress in the characterization of mouse and human mammary stem and progenitor cells has provided new insight into the regulation of their developmental hierarchy. In this review, we discuss the parameters that distinguish stem and progenitor cells from differentiated cells, as well as the signal transduction pathways that drive multilineage expansion. Lastly, we present the utility of modulating stem cell self-renewal through the use of inhibitors of the Notch and Wnt pathways.