The natural course of untreated metastatic liver disease is poor. Data from the 1960s and 1970s show that the median survival of patients receiving no treatment ranges between 3 to 12 months, with an overall median survival of 7 months.18 Liver resection provides the most favorable outcomes in appropriately selected patients. With the advancements in surgical, anesthetic, and perioperative care and in medical imaging, which allow better patient selection and surgical planning, liver resections have become accepted as standard therapy.19 Increasingly, aggressive resections are being performed with an operative mortality less than 5%. At many centers, more than two-thirds of resections now consist of major hepatectomies. While the liver resection has been accepted to be the only treatment with a chance of long-term survival in patients with CRCLM, the resectability rate of metastases at the time of diagnosis has been low, accounting for the low proportion of patients who may benefit from a surgical approach. Until recently, patients initially considered as having unresectable disease were treated with palliative chemotherapy, with poor response rates and obviously little chance of 5-year survival. Chemotherapy as a first-line treatment of metastatic colorectal cancer has greatly changed within the last decade. Oxaliplatin- and irinotecan-based combination regimens have improved the efficacy of systemic treatment. The new combination regimens not only allow increased patient survival in a palliative setting but also offer the possibility of cure to patients with previously unresectable disease with liver surgery after tumor downsizing.20- 22 By reconsidering the initial unresectability for patients who strongly respond to chemotherapy, Adam et al23 have shown that survival could be achieved by liver resection in a significant proportion of patients otherwise destined to a poor outcome. This group analyzed a consecutive series of 1439 patients with CRLM managed in a single institution during an 11-year period (1988-1999). Metastatic disease was determined to be resectable in 335 (23%) of the patients at initial presentation. The remaining 1104 (77%) were treated by chemotherapy, involving new-generation protocols. Among 1104 patients with unresectable disease, 138 (12.5%) underwent secondary hepatic resection after an average of 10 courses of chemotherapy. Seventy-five percent of procedures were major hepatectomies. Portal embolization and ablative treatments were liberally used as adjunct modalities. Currently, an average 5-year overall survival rate of 33% has been achieved with wide use of successive hepatectomies and extrahepatic resections. These results indicate that a multimodality approach with aggressive surgical and nonsurgical interventions can be justified toward the goal of improving the survival of patients with CRCLM. Also, a significant number of tumors can be downsized and patients can undergo a potentially curative resection provided that a successful neoadjuvant strategy can be used.