The rapid pace of progress in molecular genetics over the past 15 years--since the seminal description of the polymerase chain reaction--has led to the identification of the genes involved in many single gene disorders. These successes in the laboratory have already led directly to clinical applications in diagnosis, pharmacogenetics, and the development of new therapies. Progress in unravelling the genetics of complex diseases has been less straightforward. However, real excitement has followed the identification of the NOD 2/CARD 15 gene as an important determinant of susceptibility to Crohn's disease.(1,)(2) Not only has this finding provided a proof of principle for the technique of genome-wide scanning in complex disorders, but the discovery also has given real insight into the primary pathophysiology involved in chronic inflammatory bowel disease. The background to this discovery and its implications form the basis for the present article.