Recent advances in understanding the genetic basis of malignant disease have been dominated by research in colorectal cancer. It has been postulated in previous studies that colorectal adenomas and cancer occur in several rare inherited syndromes and more commonly as sporadic cases. However, new evidence suggests that inherited susceptibility may also be important in a large fraction of so-called sporadic cases. These discoveries will, in very near future, inevitably lead to radical changes in the clinical management of this disease, particularly with the introduction of molecular diagnostic procedures, new chemoprevention protocols, and possibly gene therapy. This review discusses the current developments in colorectal cancer genetics which will be central to such changes.