Traditional therapeutic regimens of solid tumors such as chemotherapy and radiotherapy often do not distinguish between malignant and normal tissues, resulting in considerable side-effects. Monoclonal antibodies (mAbs), targeted against antigens dysregulated in cancers, have therefore generated great interest in both clinical and research settings. The antibodies are either chimeric or human(ized) and can bind to and inhibit target proteins overexpressed in both solid tumors and hematological malignancies. Some of these mAbs have shown efficacy in patients who are refractory to traditional chemotherapy. Examples of FDA approved antibodies against metastatic colorectal cancer include cetuximab, panitumumab and bevacizumab. This review summarizes the current knowledge of mAbs targeting growth factors in colorectal cancer and the importance of carefully screening patients to select candidates who will benefit most from these therapies.