The article is intended to provide an overview of the strengths and limits of controlled trials of pharmacological treatment of NAFLD. No drug has so far been approved, although validated on histological outcomes. Several new drugs are under scrutiny, acting with different mechanisms along the chain of events from fatty liver to fibrosis, cirrhosis and hepatocellular carcinoma. We need to know which drug, if any, should be preferred for a tailored intervention in individual patients, according to age, comorbidities and disease severity, and if treatment should be continued lifelong, to prevent disease progression and long-term occurrence of cirrhosis.