Genomics of breast cancer is paving the way towards more and more tailored treatments. The number of molecularly targeted therapies under development is increasing. In parallel, the high-throughput analyses revealed the molecular heterogeneity of disease, and identified several very different molecular subtypes, numerous and sometimes very scarce molecular alterations, and multigenic signatures predictive for clinical outcome, some of which are being tested in prospective clinical trials. This molecular segmentation of breast cancer and the multitude of new drugs to be tested (alone and in combination) lead to develop clinical trials based on the molecular profile of tumors to guide the patient towards the most suitable drug.