Central obesity represents the major factor responsible for NAFLD, but several immunological and endocrinological mechanisms are involved in fatty infiltration in the liver, inflammation and fibrosis. Gut microbiota and genetic factors were recently indicated as major players in liver injury. Loss of weight and physical activity represent till now the cornerstone of treatment, but they are very difficult to obtain and to maintain. Several pharamocotherapeutic approaches including insulin sensitizers, omega-3 fatty acids and vitamin E have been extensively studied in randomized trials, but final conclusions still could not be formulated. Therefore, new treatments based on pathogenetic mechanisms leading to NAFLD are under evaluation to establish the effective pharmacological therapy of this disorder.