Genomewide association studies (GWAS) are being reported for an increasing number of common diseases, including first reports on GWAS for hepatobiliary diseases. Most common liver diseases are multifactorial (complex) diseases that are modified by higher-order interactions between multiple genetic and environmental risk factors. The aim of GWAS is to identify the genetic risk factors contributing to disease susceptibility and/or progression. In GWAS, large patient cohorts are genotyped for genetic markers that cover the whole genome, and genotypes are associated with phenotypes by contingency tests and regression analyses. Recent GWAS have identified "risk genes" for gallstones, fatty liver, primary cholestatic liver diseases and chronic hepatitis C virus (HCV) infection as well as fibrosis progression in HCV-infected patients. For the latter patients, "gene signatures" were developed that are composed of multiple risk variants and are associated with progressive liver fibrosis. Furthermore, mouse models are an important tool to identify novel genetic determinants of complex liver diseases. In large experimental crosses of susceptible and resistant inbred mouse strains, phenotypes are correlated with genome-wide markers by genetic linkage analyses. The findings from genome-wide studies in mice and men may contribute to a better understanding of the pathogenesis of complex liver diseases and provide a framework for the development of "personalised" strategies for prediction, early prevention and therapy.