Following the epidemics of obesity due to the consumption of high-calorie diet and sedentary lifestyle, nonalcoholic fatty liver disease (NAFLD) is now the leading cause of liver disease in Western countries. NAFLD is epidemiologically associated with metabolic syndrome and insulin resistance, and in susceptible individuals it may progress to cirrhosis and hepatocellular carcinoma. Genetic factors play a key role in NAFLD predisposition by interacting with nutritional and other environmental factors. To date, there is no drug therapy for the treatment of NAFLD, and the main clinical recommendation is lifestyle modification. In the last years, nutrigenomics is promoting an increased understanding of how nutrition affects the switch from health to disease by altering the expression of an individual's genetic makeup. The present review tries to summarize the most recent data evidencing how the interactions between nutrients and genetic factors can influence NAFLD development. The final goal should be to develop tools to quantify these complex interactions. The definition of a "nutrigenomic risk score" for each individual may represent a novel therapeutic approach for the management of NAFLD patients.