Colorectal cancer is the second leading cause of cancer-related deaths in the Western world. Recently, improvements have been made in treating patients with advanced colorectal cancer; however, response rates still remain low at only 40–50% following combination therapy. The major limitation in treating these patients is the development of drug resistance. Therefore, there is a need to identify which patients will respond to a given chemotherapy regime so that they will be spared the unnecessary time and toxicity of being placed on a regime from which they will derive no benefit. It is also widely accepted that exposure to these chemotherapies themselves can induced acute resistance. Recent developments have been made in predicting response to chemotherapy using global approaches, with the ultimate aim of individualising patient treatment and improving overall survival rates.