Insulin resistance, abdominal obesity, and inflammation play important roles in the pathogenesis of nonalcoholic fatty liver disease (NAFLD). Several adipokines, particularly adiponectin but also leptin, resistin, irisin, ghrelin, and visfatin modulate these pathogenetic mechanisms and appear to play a role in the development of hepatic steatosis and the progression to steatohepatitis and cirrhosis. Accordingly, these adipokines might represent attractive targets in patients with NAFLD. Notably, both lifestyle changes and many pharmacological agents that are used in the management of NAFLD, particularly pioglitazone and statins, exert favorable effects on adipokine levels. However, it is unclear whether these effects play a role in the improvement in liver histology. Therefore, mechanistic studies are needed to clarify the contribution of changes in adipokine levels to the effects of these interventions on hepatic steatosis, inflammation, and fibrosis. In parallel, the development of novel agents that specifically target adipokine levels might offer additional insights into the potential role of adipokines as therapeutic targets in NAFLD. Hippokratia 2016, 20(4): 259-263.