RG7204 (PLX4032) is a small molecule inhibitor that selectively blocks the activity of oncogenic BRAF^V600E kinase. The BRAF^V600E mutation is common in several human cancers, with especially high prevalence in melanoma. In the present study, Yang and colleagues describe the effect of RG7204 on tumor cells. RG7204 suppresses ERK activation and cellular proliferation in tumor cells with BRAF^V600E but not in cells expressing only wild-type BRAF. Significantly, RG7204 treatment caused partial or complete tumor regressions and improved survival of animals bearing BRAF^V600E tumors, demonstrating potent antitumor activity. These preclinical efficacy data generated in several melanoma xenograft models have foreshadowed the clinical results observed in a multi-center Phase I trial that has been enriched with metastatic melanoma patients testing positive for the BRAF^V600E mutation. For details, see the article by Yang and colleagues on page 5518 of this issue.