Metastatic colorectal cancer represents an incurable condition, with the exception of a very select group of patients in whom surgical excision of recurrent disease is possible. Chemotherapy offers a significant palliative benefit and may prolong patient survival. The preferred cytotoxic agent is 5-fluorouracil, through the optimal administration schedule is unknown. Recent evidence also supports the use of second-line chemotherapy for patients who develop progressive disease following 5-fluorouracil treatment. Promising results have been obtained with new drugs, in particular oxaliplatin and irinotecan. Novel therapeutic approaches, including immunotherapy and liver directed strategies, are undergoing clinical evaluation. Comprehensive supportive care, with appropriate community and hospital based palliative care, is essential in the management of patients with advanced colorectal cancer.