Chronic liver disease has globally risen mainly due to a prevalent Hepatitis C Virus (HCV) infection rate and an epidemic of obesity. It is estimated by the year 2030, 2.2 billion people around the world will be overweight and 1.1 billion people will be obese. Diabetes and obesity are the main risk factors for the development of the metabolic syndrome and in the liver of Non-Alcoholic Fatty Liver Disease (NAFLD) which could progress to NASH related cirrhosis and liver malignancy. At present there is not effective therapy for NASH besides loss of weight and exercise. Furthermore, optimal management of HCC with curative intent includes resection or liver transplantation. Therapies that is limited due to the degree of liver dysfunction, medical conditions at the time of diagnosis and the scarcity of available liver grafts. The role of cellular lipid management and metabolism in human health and disease is taking a center stage. The present overview articulates the current pathophysiology of fatty liver disease under the aging processes, potential biological markers of liver disease diagnosis and progression and future therapies.