Genetic risk factors play critical roles in liver injury and fibrosis, since both initiation and progression of chronic liver diseases differ between individuals challenged by identical environmental factors. Recently genomewide association studies have identified specific novel risk genes for (non-alcoholic) fatty liver disease (adiponutrin), viral hepatitis (interleukin 28B), and chronic cholestatic diseases (interleukin 12). Here, we summarize these studies and provide an inventory of the susceptibility genes. In the future, risk assessment of complex liver diseases might be based on polygenic risk scores or even gene networks. Complimentary to study in humans, experimental crosses of inbred mouse strains contribute to the genetic dissection of gene-gene interaction and gene-environment interactions. The results of these genomewide studies in mice and men might open new avenues for the prevention and treatment of chronic liver injury and the regression of liver fibrosis.