Aims: This review aims to provide a straightforward conceptual framework for the knowledge and understanding of Metabolic dysfunction-associated steato tic liver disease (MASLD) in the broad spectrum of steatotic liver disease and to point out the need to consider metabolic dysfunction and comorbidities as interrelated factors for a holistic approach to fatty liver disease. Data synthesis: MASLD is the new proposed term for steatotic liver disease that replaces the old terminology of non-alcoholic fatty liver disease. This term focused on the relationship between metabolic alteration and hepatic steatosis, reflecting a growing comprehension of the association between metabolic dysfunction and hepatic steatosis. Numerous factors and conditions contribute to the underlying mechanisms, including central obesity, insulin resistance, adiponectin, lipid metabolism, liver function, dietary influences, the composition of intestinal microbiota, and genetic factors. The development of the condition, however, involves a more intricate network of components, such as neurotensin and Advanced Glycation End Products, highlighting the complexity of its pathogenesis. Conclusions: MASLD must be regarded as a complex clinical problem in which only a holistic approach can win through the coordination of multi-professional and multi-speciality interventions. (c) 2024 Published by Elsevier B.V. on behalf of The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University.