Non-alcoholic fatty liver disease (NAFLD) is increasingly recognized as the most common cause of chronic liver disease worldwide, with a global prevalence of 25.2%. The high burden of NAFLD extends beyond liver diseases, as patients are at risk of developing not only liver related conditions, including cirrhosis and hepatocellular carcinoma, but also cardiovascular complications associated to metabolic syndrome. The present special issue of The Spanish Journal of Gastroenterology (Revista Española de Enfermedades Digestivas) focusses on diverse key aspects of NAFLD, including characterization of fecal microbiota profiles, the role of bariatric endoscopy, evaluation of suitable pre-clinical models for NAFLD or differential epidemiological risk factors associated to NASH and fibrosis.