Nonalcoholic fatty liver disease (NAFLD) is one of the most common etiologies of chronic liver disease worldwide. NALFD encompasses a continuum of histological findings ranging from steatosis alone, to nonalcoholic steatohepatitis (NASH) with steatosis, inflammation, hepatocyte ballooning, fibrosis and eventually liver cirrhosis. The pathogenesis of NAFLD might be related to a deregulated cross-talk between liver and visceral adipose tissue, originating an impairment of normal insulin signaling. A better comprehension of the immunologic and metabolic roles of adipose tissue in modulating inflammatory pathways will enhance our understanding of the molecular mechanisms leading to progression of fatty liver disease. These insights, moreover, will suggest new strategies to improve insulin sensitivity and reduce obesity-associated morbidities and mortality.