The need for improved systemic therapy for breast cancer is great. Cancer growth represents an imbalance between cell proliferation and cell death: thus, effective anti-cancer therapies may act to decrease cell proliferation or increase cell death, or both. This chapter delineates the role of the programmed cell death process in maintaining homeostasis in normal mammary tissues. The preservation of such death pathways in malignant mammary cells and the ability of chemotherapeutic agents to initiate the programmed cell death process in these cells is reviewed. Finally, ongoing research exploring new ways to take advantage of these death pathways in the clinical setting is examined.