One of the most impressive changes in the therapeutic landscape of breast cancer in the past decade has been the advent of targeted therapies for specific subtypes. This article discusses the meaning of targeted therapy and examines the genomic basis for targeted therapy as it has emerged over the past decade. Human epidermal growth factor receptor 2 (HER2)-targeted therapy, the principle example of targeted therapy to enter the adjuvant arena in the past decade, is described in depth. Novel targeted therapies under development, many currently being examined in the adjuvant setting, are also explored, including anti-vascular endothelial growth factor therapy, poly (ADP ribose) polymerase (PARP) inhibition for triple-negative breast cancers, and agents targeting site-specific metastasis to the bone (receptor activator of NF-kB [RANK] ligand inhibition). Chemotherapy, the epitome of nonspecific anticancer therapy, is in the process of becoming targeted therapy as understanding of breast cancer biology improves.