Advanced colorectal cancer is a significant cause of worldwide cancer-related mortality. For the majority of patients, palliative chemotherapy can yield substantial improvements in survival. Fluorouracil has been the mainstay of treatment in this setting for the past few decades. The relatively recent availability of new combinations with active agents such as irinotecan and oxaliplatin makes this a promising and hopeful time for the treatment of metastatic colorectal cancer, with median survivals now approaching 18-21 months. For patients presenting with resectable metastases, the goal of therapy is surgery with a curative intent. There exists the potential for this approach to be extended also to a greater proportion of patients whose cancer may be rendered resectable following effective neoadjuvant chemotherapy. In addition, an improved understanding of molecular predictors for treatment response and toxicity may facilitate the future selection of individualised treatments for a given tumour profile. Further improvements in the management of advanced disease will continue to be pursued through the ongoing development of multimodality approaches and the incorporation of novel targeted agents with innovative chemotherapy combinations.