An increasing number of clinical and experimental investigations indicate that some xenobiotics are able to aggravate the nonalcoholic liver diseases (NAFLD) that are frequently associated with obesity. Indeed, different drugs, some industrial compounds and alcohol intoxication can major fatty liver, or accelerate the progression of fatty liver into nonalcoholic steatohepatitis. Moreover, because of an increased activity of several hepatic cytochromes P450 during NAFLD, some xenobiotics can more easily be transformed into toxic metabolites and induce severe acute liver injury. Clinical studies and experimental research are now needed to identify all the xenobiotics that can be particularly hepatotoxic in the context of obesity and to assess the different mechanisms of such higher susceptibility. This is a major issue if one considers the alarming prevalence of obesity in numerous countries, as well as the high number of drugs prescribed to obese patients in order to treat their different dysmetabolic diseases. (C) 2013 Elsevier Masson SAS. All rights reserved.