Long-term survival with colorectal liver metastases (CLM) usually requires surgical resection, despite considerable improvements in systemic chemotherapy that have extended median survival with metastatic colorectal cancer from 6 months to in excess of 2 years. Multidisciplinary management is now the norm in the perioperative setting, and chemotherapy has become part of an accepted treatment paradigm. Systemic and intrahepatic chemotherapy can shrink inoperable disease to the point of resection, and a combination of neoadjuvant and adjuvant chemotherapy improves disease-free survival for patients with operable CLM. A greater understanding of the biology of colorectal metastasis has revealed many new potential targets, and carefully designed clinical trials are required to investigate these and other existing biologic therapies in this setting. In this article we discuss the biology of colorectal cancer metastases, the rationale for perioperative chemotherapy, and the recent and ongoing investigation of perioperative chemotherapy in the management of CLM.