Non-alcoholic fatty liver disease (NAFLD) has moved rapidly to the forefront of clinical disease, with a prevalence of 30% in the adult United States population and a definite but yet uncertain rate of progression to cirrhosis and end-stage liver disease. This disease has an impact on all areas of clinical medicine, with increasing prevalence and adversity. It is essential to understand the pathophysiologic mechanisms involved in NAFLD, so that therapeutic strategies can be developed. Although fatty liver may be caused by other factors, this review concentrates on fatty liver associated with insulin resistance, sometimes referred to as the primary form.