Triple-negative breast cancer (TNBC) accounts for approximately 15% of breast cancer diagnoses, and exhibits substantial overlap with basal-type and BRCA1-positive breast cancer. In recent years, a greater understanding of the biology of this disease has led to the development of numerous and varied therapeutic approaches. Neoadjuvant trials using conventional cytotoxic agents such as cisplatin have demonstrated TNBC to be a relatively chemo-sensitive disease. In the current review, focus is directed towards novel targeted strategies for TNBC. Recent trials have shown the poly(ADP-ribosyl)ation polymerase (PARP) inhibitors BSI-201 and olaparib to be highly effective in TNBC and BRCA1/2-positive disease, respectively. Efforts to assess the role of antiangiogenic agents such as bevacizumab and sunitinib in TNBC are ongoing. Finally, preclinical studies provide a signal of potential activity with use of heat shock protein 90 (Hsp90) and Src inhibitors in this breast cancer subtype.