In the Western world, nonalcoholic fatty liver disease(NAFLD) is considered as one of the most significant liver diseases of the twenty-first century. Its development is certainly driven by environmental factors, but it is also regulated by genetic background. The role of heritability has been widely demonstratedby several epidemiological, familial, and twin studies and case series, and likely reflects the wide interindividual and inter-ethnic genetic variability in systemic metabolism and wound healing response processes. Consistent with this idea, genome-wide association studies have clearly identified Patatin-like phosholipase domain-containing 3 gene variant I148 M as a major player in the development and progression of NAFLD. More recently, the transmembrane 6 superfamily member 2 E167 K variant emerged as a relevant contributor in both NAFLD pathogenesis and cardiovascular outcomes. Furthermore, numerous casecontrol studies have been performed to elucidate the potential role of candidate genes in the pathogenesis and progression of fatty liver, although findings are sometimes contradictory. Accordingly, we performed a comprehensive literature search and review on the role of genetics in NAFLD. We emphasize the strengths and weaknesses of the available literature and outline the putative role of each genetic variant in influencing susceptibility and/or progression of the disease. In the Western world, nonalcoholic fatty liver disease (NAFLD) is considered as one most of liver diseases of the twenty-first century. The role of heritability has been substantially demonstrated by several epidemiological, familial, and twin studies and case series, and likely reflects the wide interindividual and inter-ethnic genetic variability in systemic metabolism and wound healing response processes. Consistent with this idea, genome-wide association studies clearly identified Patatin-like phosholipase domain-containing 3 gene variant I148 M as a major player in the development and progression of NAFLD. More recently, the transmembrane 6 superfamily member 2 E167 K variant emerged as an relevant contributor in both NAFLD pathogenesis and cardiovascular outcomes. Furthermore, numerous casecontrol studies have been performed to elucidate the potential role of c and emphasize the strengths and weaknesses of the available literature and outline the putative role. of each genetic variant in influencing susceptibility and / or progression of the disease.