Our understanding of the molecular heterogeneity and pathogenesis of breast cancer has led to significant improvements in patients' survival. The observation of steroid hormone dependence has led to the successful implementation of tamoxifen, aromatase inhibitors and other estrogen receptor modulators in both the adjuvant and advanced setting. Similarly, the observation of HER2 amplification and the successful targeting of HER2 with trastuzumab, and more recently lapatinib, have improved the outcome for this subgroup of patients as well. Still, there is a group of women that represent approximately 15-20% of breast cancer diagnoses that do not demonstrate evidence of estrogen receptor or progesterone receptor expression, or HER2 amplification, which often has an aggressive clinical course dictated, not only owing to its underlying biology, but also due to the lack of treatment options available other than chemotherapy. Recent advances in our ability to analyze clinical tissue has allowed for genome-wide screening in an attempt to identify the driving molecular alterations in this subgroup. These studies are increasing our understanding of this group and are leading to the integration of new therapeutic approaches in this disease. In reality, the classification of 'triple-negative' defines this group by the absence of something 'positive'. Here, we will review the current molecular understanding of 'triple-negative' breast cancer and highlight current clinical research in this challenging group of patients.