Liver metastases occur in approximately 60% of patients with colorectal cancer. Liver resection is currently the only treatment that offers long-term survival. The 5-year survival rates range from 25 to 40%; however, less than 20% of patients are candidates for resection. The prognosis for the remaining patients is grim, since palliative chemotherapy and symptomatic care are the only available options. The ability to transfer therapeutic genes to target cells in vivo has opened up unprecedented possibilities for the management of metastatic liver cancer. A large number of genes with therapeutic potential have been cloned. Families of genes currently used can be classified as "suicide", cytokine, anti-angiogenic, tumour-suppressor, and oncogenes. Physico-chemical and, more commonly, viral vectors can be used to enhance gene transfer into tumours. The delivery systems for gene therapy continue to improve as minimally invasive techniques are combined with recent vector technology. Encouraging results, such as tumour destruction and long-term protective immunity against metastatic disease, have been obtained in different animal models. This article discusses several recent phase I and II clinical trials. The results of these combined laboratory and clinical studies are expected to define optimal means of incorporating gene therapy into the treatment of liver metastasis.