Although the recent advances in therapeutic drugs have improved outcomes for multiple myeloma, this disease remains incurable. One of the most commonly detected genetic abnormalities in myeloma is the activating oncogenic mutation of KRAS and NRAS in MAP kinase pathway. New technologies, such as next generation sequencing, have revealed an activating mutation in BRAF, as well; this mutation is observed in a half of all melanoma patients. BRAF and MEK inhibitors have been used for treating resistant melanoma with the BRAF V600E mutation. It is reported that a refractory myeloma patient with this mutation who was treated with BRAF inhibitor vemurafenib achieved a partial response. Although there have been no satisfactory results for clinically effective inhibitors of signal transduction molecules yet, novel drugs targeting this mechanism are expected to be useful as therapeutic agents against myeloma in the future.