Great strides have been made in improving the outcome of patients with metastatic colorectal cancer and targeted agents are an important part of the treatment arsenal. The approved monoclonal antibodies, bevacizumab, cetuximab and panitumumab, are part of the standard of care, yet only recently have we begun to define which patients benefit from these therapies using predictive tumor biomarkers. More recently, novel agents including aflibercept and regorafenib have had promising results and may become approved therapies. In addition, agents targeting the mTOR pathway and the TNF pathway have demonstrated early evidence of benefit. In the coming years, we may experience an influx of new therapies, possibly leading to further prolongation of patient survival or even, for some, a cure.