**Abstract**

Until fairly recently, treatment options for advanced melanoma have been relatively limited. Fortunately, the last decade has seen dramatic improvements in response rates and duration of overall survival after the introduction of checkpoint inhibitors and targeted therapies against mutations in the B-isoform of Raf (B-Raf) in metastatic or inoperable melanoma. This book chapter will discuss the role of wild type B-Raf in the cell, the changes induced by mutations in this protein, and current FDA approvals for targeted therapies against B-Raf, both as a monotherapy and in combination with MEK inhibitors. We will also summarize mechanisms of resistance against these targeted therapies as well as novel therapeutic regimens proposed to bypass resistance.

**Keywords:** melanoma, metastasis, B-Raf, MEK, targeted therapy, adjuvant
