Understanding the genetic basis of ‘‘complex disease’’has been heralded as one of the major challenges of the post genome era. 1 However what are ‘‘complex diseases’’and how will understanding the genetics of such diseases advance medical science? There has been a great deal of ‘‘hype’’about the potential of the human genome mapping project. 2 The three major claims are that this information will:(a) be used in diagnosis;(b) provide useful prognostic indices for disease management (including the development of individualised treatment regimens, based on the findings of both immunogenetic and pharmacogenetic studies); and (c) provide insight into the pathogenesis of these diseases. Of these three objectives the last has the greatest potential and is the least exaggerated claim. In this review I shall highlight major associations, discuss some of the practical issues that arise, and outline how current knowledge of the immunogenetic basis of chronic liver disease is beginning to inform the debate about disease pathogenesis.