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One of the goals of personalized medicine is to utilize biomarkers to sub-classify patients into risk groups that can be used to guide recommendations for therapy. In addition to classical risk factors, gene signatures and genomics are being developed as a means to biologically characterize tumors and to stratify patients according to the risk associated with the specific molecular aberrations present in their disease. Gene signatures and genomics are currently being investigated as a personalized medicine strategy for many cancers, but have been studied most extensively in breast cancer. In this disease, the results of genetic signatures have come to influence current recommendations for adjuvant chemotherapy for appropriately selected patient populations. In this chapter, we will review the use of gene signatures and genomics in the development of personalized oncology, with an emphasis on applications for breast cancer.