Colorectal cancer is the second commonest malignancy in the western world, accounting for 20,000 deaths in the U.K. per year. Over the last 10 years, great strides have been made in our understanding of the molecular controls governing the transition from normal mucosa, through adenoma, and finally to carcinoma. This review focuses on the recently discovered DNA mismatch repair pathway and its role in the development of both sporadic and an inherited form of colorectal cancer, namely hereditary non-polyposis colorectal cancer (HNPCC).