Cardiac and hepatic fat are associated with insulin resistance and impaired suppression of lipolysis, ultimately leading to lipotoxicity. In the heart the lipotoxic effect translates into an impairment of energetic and mechanical efficiency, whereas in the liver a fibrogenic response is favored by the abundance of inflammatory cells. These features precede, and likely contribute to, left ventricular overload and cardiac hypertrophy through mechanisms similar to the ones observed in the progression of liver damage in nonalcoholic fatty liver disease (NAFLD). Collectively these findings suggest the presence of complex and intertwined interrelationships between NAFLD, myocardial steatosis, and coronary artery disease.