Cryptogenic cirrhosis represents the third cause of cirrhosis in Mexico and comprises the clinical spectrum of NAFLD. Insulin resistance is the main factor in NASH development, as well as genetic and environmental factors. Derangement in insulin signaling pathways, either pre-receptor or post-receptor, causes insulin resistance (IR). The post-receptor dysfunction represents the primary cause of IR and links with metabolic syndrome, mainly diabetes and obesity. Prevailing metabolic moment will establish the IR status. NASH progression causes fibrosis, cirrhosis and hepatocelular carcinoma. Therapy is currently directed at treating components of the metabolic syndrome which may be beneficial for the liver. Through different mechanisms IR originates to fat deposit in liver and subsequently under oxidative stress and pro-inflammatory cytokines and then to inflammatory infiltrate, fibrosis and finally cirrhosis. This review focuses on insulin resistance and the related mechanisms of hepatic damage.