For patients with unresectable colorectal liver metastases (CRLM), selection of adequate drug combinations, with or without biological agents, for immediate use is crucial for success of conversion to resectable CRLM with potentially curative results. This paper addresses the use of biological agents directed against the two main targets in colorectal cancer—vascular endothelial growth factor (VEGF) and epidermal growth factor receptor (EGFR). Addition of the anti-angiogenic monoclonal antibody (MAb) bevacizumab to chemotherapy may increase resection of CRLM for patients with KRAS mutated or for unselected patients. Caution must be exercised with wound healing complications when surgery is performed after bevacizumab use. Patients with KRAS wild-type should be considered for combination therapy with EGFR inhibitors, because this strategy has led to promising results with improved R0 resection.