Breast cancers that are negative for estrogen receptor (ER), progesterone receptors (PR) and HER2, using standard clinical assays, have been dubbed triple-negative (TN). Unlike other molecular subtypes of invasive breast cancer, validated targeted therapies are currently unavailable for patients with TN breast cancer. Preclinical studies however, have identified several potential targets such as epidermal growth factor receptor (EGFR), SRC, MET and poly ADP ribose polymerase 1/2 (PARP1/2). Because of tumor heterogeneity, it is unlikely that any single targeted therapy will be efficacious in all patients with TN breast cancer. The rational way forward for treating these patients is likely to be biomarker-driven, combination targeted therapies or combination of targeted therapy with cytotoxic chemotherapy.