Colorectal cancer is the second most commonly diagnosed cancer and also the second most common cause of death from cancer in Australia. This is despite colorectal cancer being one of the most preventable and curable cancers; a large proportion of all cases could be prevented by appropriate screening (and polypectomy) or, if discovered in the early stages, could be treated by surgery alone. However, screening everyone is not appropriate since people are not at equal risk of colorectal cancer as it is a composite of differences in lifestyle and environmental factors as well as a substantial variation in underlying familial and genetic susceptibility. Colorectal cancer screening will be most effective if it can be applied proportionately to individual person’s risk of the disease. To enable targeted screening, new prediction tools are needed to enable personalised risk assessment by taking into account all risk factors for the disease, and the most promising risk factor yet to be considered is genomic risk. Personalised risk-based screening will be a new precision medicine paradigm for reduction in colorectal cancer burden.