Non-alcoholic fatty liver disease (NAFLD) is the hepatic manifestation of metabolic syndrome and can progress to cirrhosis, liver failure, and hepatocellular carcinoma. In the last two decades, the prevalence of NAFLD has been growing in most developed countries, mainly as a consequence of its close association with obesity and diabetes mellitus. The exact pathogenesis of NAFLD and especially the mechanisms leading to disease progression have not been completely understood. Adipocytes produce and secrete several bioactive substances known as adipocytokines which are implicated in the pathogenesis of the disease. Among them, adiponectin is an insulin-sensitizing adipocytokine possessing multiple beneficial effects on obesity-related medical complication. This review focuses on the role of adiponectin in NAFLD pathogenesis and its potential use as a diagnostic tool but also as therapeutic target for NAFLD management.