The increasing prevalence of obesity in Western countries has led to a significant increase of nonalcoholic fatty liver disease (NAFLD) over the past decades. Being part of the metabolic syndrome, NAFLD is thought to be the most frequent cause of elevated liver enzymes in the United States affecting up to one third of the population. NAFLD is also proposed to be the major cause for cryptogenic cirrhosis and hepatocellular cancer of unknown etiology, and thus, represents one of the most important problems for hepatologists in the future. However, the natural course of NAFLD is highly variable and is influenced by both environmental and genetic factors. Polymorphisms in specific genes have been proposed to increase the risk of fibrosis in patients with NAFLD. The present review article summarizes currently available data from genotype-phenotype studies and defines candidate genes that deserve future investigation.