Genomic studies have shown that breast cancer includes a large number of targetable genomic alterations. Most of these genomic alterations are rare and can evolve during the natural history of the disease. Three paths are being followed to develop precision medicine in metastatic breast cancer. First, the conventional path will consist of fragmenting the disease and developing drugs in each rare genomic segment. This will require screening large numbers of patients for genomic alterations to run the therapeutic trials, especially the registration trials. The second path will consist in clustering rare genomic alterations in more frequent segments defined by an altered pathway. Finally, one possible path for precision medicine will be to test genomic algorithms for the whole patient population with metastatic breast cancer. This latter scenario would reunify breast cancer into a single entity and test whether the use of genomics would improve outcomes in this population of patients. Challenges and perspective in the field of precision medicine will include the prediction of resistance, the integration of immunology, and DNA repair in the genomic algorithms and the transfer of concepts to early-stage breast cancers.