New generation ATP-competitive Raf inhibitors, such as the clinically approved vemurafenib (PLX4032) [93–97] and dabrafenib (GSK2118436) [96,98], have improved selectivity for mutant B-RafV600E (Table 1), resulting in high response rates and increased progression-free and overall survival in patients with BRAF mutant melanoma. The gene discussed is BRAF; the disease is melanoma.