Non-alcoholic fatty liver disease (NAFLD) is a common disorder and its prevalence is expected to increase due to the rising incidence of type 2 diabetes mellitus (T2DM) and obesity. NAFLD is associated with increased mortality rates and cardiovascular disease is the leading cause of death in these patients. The pathogenesis of NAFLD is not completely elucidated but insulin resistance and oxidative stress appear to play a major role. NAFLD is more prevalent and more severe in patients with T2DM. A multitude of pharmacological agents have been evaluated in NAFLD but most studies were small, short-term and yielded unsatisfactory results in terms of efficacy. Patients with T2DM and NAFLD appear to be even less responsive to the evaluated agents. Thus, the optimal management strategy for NAFLD remains unclear. On the other hand, preliminary data suggest that lifestyle intervention can reduce the incidence of NAFLD in overweight or obese patients with T2DM. Accordingly, prevention of obesity and T2DM is of paramount importance for the reduction of the prevalence of NAFLD and of its associated cardiovascular and liver-related complications.