Non-alcoholic fatty liver disease is now recognized as a cause of potentially progressive liver damage, posing patients at risk of advanced liver failure. Unfortunately, the natural history of disease is only partly known, the disease is slowly progressive and therapeutic outcomes are difficult to define. These factors have limited therapeutic trials to pilot studies, and very few randomized-controlled studies are available. The concept that insulin-resistance, coupled with oxidative stress, may be the underlying mechanism responsible for fat accumulation and disease progression points to insulin-sensitizing agents (metformin, thiazolidinediones) as the most promising drugs. They proved effective in reducing enzyme levels in the short period, but very limited information is available on liver histology, not to say progression to liver cell failure. Large, long-term, placebo-controlled randomized studies are eagerly awaited. Outside controlled studies, nutritional counselling and physical exercise aimed at moderate weight loss remain the basis of any therapeutic intervention.