Metastatic breast cancer continues to be a life-threatening diagnosis that impacts hundreds of thousands of patients around the world. Targeted therapies are usually associated with less toxicity compared with cytotoxic chemotherapies and often induce response or durable disease control in estrogen receptor (ER) and/or HER2+ breast cancers. Drugs that target CDK 4/6 either alone or in combination with endocrine therapy have demonstrated substantial improvements in progression-free survival (PFS) compared with endocrine monotherapy. Most recently, PARP inhibitors have shown longer PFS compared with physician's choice of chemotherapy in BRCA-associated cancers, leading to the first U.S. Food and Drug Administration (FDA) approval of a targeted therapy with the potential to benefit a subgroup of patients with triple-negative breast cancer (TNBC). Finally, newer drug delivery strategies using antibody drug conjugates have also allowed a "targeted approach" to deliver moderate to extremely potent cytotoxins directly to sites of metastatic disease, with less toxicity.