Triple negative breast cancer (TNBC) is an aggressive subtype of the disease against which targeted therapies that significantly improve the prognosis for hormone receptor-positive and HER2-overexpressing breast cancers are ineffective. This article summarizes our current understanding of the biology of TNBC as it relates to the efficacy of standard and investigational therapies. It reviews promising preliminary results that have been achieved with chemotherapeutic agents including the platinum analogs and agents that inhibit DNA repair by targeting poly ADP-ribose polymerase (PARP), while anti-angiogenic therapies and those that target the epidermal growth factor receptor (EGFR) have had more limited success. Agents that target a number of other pathways which appear to influence the biologic aggressiveness of TNBC, including src and PI3K, are in early stage clinical trials. As we learn more about TNBC, and which of its characteristics determine treatment response and resistance, we should become better able to select appropriate therapies for biologically defined patient subgroups, and reduce the clinical burden of this disease.