Recently there have been significant advances in rational drug design for the treatment of breast cancer, especially in the area of targeted drug therapy. These include drugs which target the HER2 receptor and angiogenesis and the novel class of drug the PARP inhibitors. Some of these agents, for example, trastuzumab used in the treatment of HER2 positive breast cancer are already established as the standard of care. However, the duration of adjuvant trastuzumab, whether to continue it beyond progression in metastatic disease and the mechanism for developing trastuzumab resistance, remain to be determined. There is also much still to be learnt regarding other targeted therapies; the efficacy of different agents, the optimal duration of use and combination of therapies. Many of these agents are already in clinical trials, the results of which are likely to change clinical practice.