Over the last few decades it has become clear that highly penetrant disease genes are responsible for a minor proportion of colorectal cancer cases. Families with hereditary syndromes are today recognized and included in surveillance programs known to reduce morbidity and mortality in colorectal cancer. Colorectal cancer is preventable and screening strategies in whole populations are currently under debate. Colorectal cancer can be considered a complex disease, with a combination of predisposing genetic variants and environmental factors that contribute to the illness as a whole. The progress made in the genome project provides an opportunity to determine such genetic variants and environmental factors. This knowledge can be used to define a subpopulation at increased risk for colorectal cancer. It will be more feasible to design preventive strategies for this subgroup than for a whole population.