Metastatic colorectal cancer (mCRC) is a prevalent disease for which many new therapies have been developed over the past decade. Currently, standard of care chemotherapeutic regimens for mCRC include doublet cytotoxic chemotherapy with or without the anti-vascular endothelial growth factor (VEGF) monoclonal antibody bevacizumab, anti-epidermal growth factor receptor (EGFR) monoclonal antibodies such as cetuximab and panitumumab with or without chemotherapy, and single-agent cytotoxic chemotherapy or targeted therapy for 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-VEGF and anti-EGFR antibody therapy, and the more novel agents ziv-aflibercept and regorafenib for treatment of mCRC. Furthermore, molecular profiling of CRC has identified several 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 CRC offers a promising future.