Without a doubt, one of the greatest promises of the human genome project has been the expectation that its completion will rapidly accelerate the discovery of the heritable components of complex disease. Such discoveries will educate us as to the underlying causes of disease and hold out great promise for medicine in the future by potentially enabling the prediction of individual risk, the selection of therapy based on genetic profile, and a more rational approach to designing drugs. Unfortunately, discovering these genetic components of complex disease has been much more difficult than initially hoped and, to date, very few positive results have been conclusively confirmed. We review here approaches to tackling the problem of gene finding in complex disease with an emphasis on new approaches that may complement and supplement existing methods that have been making only slow progress toward the elucidation of the genetic architecture of disease. Along the way we highlight the successful work by many groups in studying the genetics of IBD, where significant successes have arrived earlier than in most other complex human diseases.