Until recently, approximately 30% of patients with resectable hepatic metastases from colorectal cancer survived 5 years after surgery. Additionally, many patients present with unresectable metastases and can look forward only to palliative care. Whereas therapeutic approaches such as cryosurgery appear to improve resectability, a key to resecting hepatic metastases is the ability to shrink the metastatic sites to make them more amenable to surgery. The administration of traditional chemotherapeutic modalities by conventional means or via intra-arterial or portal vein infusion has not provided significant improvements. The recent introduction of the combination oxaliplatin-5-fluorouracil/folinic acid administered as a chronomodulated regimen, however, has provided better response rates with minimal toxicity. Recent results show that the resection of previously unresectable metastases became possible in up to 16% of patients after chemotherapy with a chronomodulated regimen of oxaliplatin plus 5-fluorouracil/folinic acid. Of the patients who had successful resections, 54% and 40% were alive at 3 years and 5 years after surgery, respectively. The results of these studies demonstrate that this new approach can significantly prolong survival for patients with a previously bleak outlook. As a result, new treatment algorithms are evolving, integrating chemotherapeutic and surgical strategies for the treatment of patients with metastatic colorectal cancer.