Metastatic colorectal cancer is a prevalent disease for which many new therapies have been developed over the past decade. Currently, standard of care chemotherapeutic regimens for metastatic colorectal cancer include doublet cytotoxic chemotherapy with or without the anti–vascular endothelial growth factor monoclonal antibody bevacizumab, anti-epidermal growth factor receptor monoclonal antibodies such as cetuximab and panitumumab with or without chemotherapy, and single-agent cytotoxic chemotherapy or targeted therapy for those patients intolerant of combination regimens. Recent studies have investigated the efficacy of triplet cytotoxic chemotherapeutic regimens, bevacizumab in combination with chemotherapy beyond first-line therapy disease progression, dual anti-vascular endothelial growth factor and anti-epidermal growth factor receptor antibody therapy, and the more novel agents ziv-aflibercept and regorafenib for the treatment of metastatic colorectal cancer. Furthermore, molecular profiling of colorectal cancer has identified a number of genetic alterations for which targeted therapies are currently being developed. Optimal drug combinations and treatment sequences have yet to be defined, but an expanding armamentarium of therapies with which to treat colorectal cancer offers a promising future.