The established BRAF- and MEK-inhibitor combinations such as vemurafenib/cobimetinib, dabrafenib/trametinib, and encorafenib/binimetinib that target this mutation and the downstream MEK enzymes have significant clinical efficacy with increased overall and disease-free progression survival over the single agent BRAF inhibitor (dabrafenib, vemurafenib, and encorafenib) as demonstrated in the Combi-D [13,14], CoBRIM [15,16], and COLUMBUS [2,17] studies, respectively, and are utilized in clinical practice in patients with advanced/metastatic melanoma and in the adjuvant setting [18]. The gene discussed is BRAF; the disease is metastatic melanoma.