In developed countries, there has been a remarkable improvement in mortality from breast cancer, but almost all of that benefit has occurred in the estrogen receptor (ER)(+) and human epidermal growth factor receptor (HER)-2(+) subsets. Triple-negative breast cancer, defined as tumors that are negative for ER, progesterone receptor, and HER-2, represent a minority of breast cancers. However, because of the poor prognosis in this particular subtype, triple-negative disease accounts for a disproportionate number of metastatic cases and breast cancer deaths. While chemotherapy is effective in triple-negative disease, research continues to better target therapies and predict prognosis. Recent studies have suggested a link between BRCA mutations and triple-negative disease, but the nature of this link remains opaque. Antiangiogenic agents such as bevacizumab have demonstrated efficacy across subtypes. More recently, poly(ADP-ribose) polymerase inhibitors appear to take advantage of the concept of synthetic lethality, or dual pathway inhibition, in attacking triple-negative and BRCA-associated tumors. These and other studies in triple-negative disease will help us to better identify effective treatment options and improve outcomes in these patients. This article addresses the nature of, and therapeutic strategies for, triple-negative breast cancer.