This review summarizes advances in our understanding of the genomic and epigenomic abnormalities in breast cancers that are being revealed by the increasingly powerful suite of genomic analysis technologies. It summarizes the remarkable genomic heterogeneity that characterizes the disease, describes mechanisms that shape cancer genomes as they evolve toward metastasis, summarizes important recurrent aberrations that exist in spite of the genomic chaos and that contribute to breast cancer pathophysiology, and describes the use of preclinical models to identify drugs that will be effective against subsets of breast cancers carrying specific genomic and epigenomic abnormalities.