Non-alcoholic fatty liver disease (NAFLD) is now the most frequent chronic liver disease in the developed countries. There is also growing evidence from basic and clinical research that NAFLD has a strong relationship to insulin resistance, which is a key factor in the development of type 2 diabetes. The aim of this review is to summarize the recent important findings linking NAFLD and insulin resistance. Lipid accumulation, particularly of diacylglycerol, appears to be of major importance in this process. Mitochondrial dysfunction, through decreased mitochondrial biogenesis, increases oxidative stress, and ageing also plays an important role. Finally, endoplasmic reticulum stress and inflammation also probably contribute to the development of insulin resistance via mechanisms that are still not well understood. Clinical aspects of NAFLD, such as its diagnosis and management, are also investigated in this review.