The BRAF inhibitor vemurafenib was approved in the United States in 2011 for patients with previously untreated, unresectable, or metastatic melanoma harboring the BRAF V600E mutation based on an improvement in OS versus DTIC in a phase III trial.18–58 With the regulatory approvals of ipilimumab and vemurafenib, critical questions have arisen for melanoma specialists regarding the use of these agents in order to optimize the benefit-risk profile for patients that harbor a BRAF mutation. The gene discussed is BRAF; the disease is melanoma.