Treatments for metastatic breast cancer are increasingly tailored towards individual tumor biology. For tumors that overexpress HER2, progressing on trastuzumab and lapatinib, a range of active agents including pertuzumab, neratinib and trastuzumab-MCC-DM1, have demonstrated activity when combined with trastuzumab. In HER2-normal metastatic breast cancer, recent studies suggest that the addition of bevacizumab to first-line chemotherapy improves progression-free survival irrespective of choice of cytotoxic agent. Another interesting area of investigation is the inhibition of poly-ADP-ribose polymerase, an enzyme important for DNA repair. This strategy may be particularly effective in patients with inherited defects in DNA repair or by the co-administration of DNA damaging cytotoxic chemotherapy. This article covers key new areas of systemic therapy for MBC from the American Society of Clinical Oncology 2009 annual meeting.