Detection of the BRAF V600E mutation has important genetic, prognostic, and therapeutic implications for patients with metastatic colorectal cancer (mCRC), identifying a subgroup of patients who derive modest benefit from standard treatments and have extremely poor prognosis. The evolution of molecular profiling and the implementation of next generation sequencing in the evaluation of a patient with BRAF-mutated mCRC has currently led to the discovery of actionable alterations. Targeting multiple pathways of resistance in BRAF-mutated mCRC may be the most efficacious route. Then, over a short period of time, the treatment landscape BRAF-mutated mCRC patients has shifted dramatically. Finally, novel treatment strategies are available. This review will discuss on currently approved treatments for BRAF V600E mutated mCRC and will try and portray the changing landscape in this setting in the era of targeted molecular therapy.