Non-alcoholic fatty liver disease (NAFLD), one of the commonest causes of chronic liver disease in the United States, represents several overlapping clinicopathological states, ranging from simple steatosis to non-alcoholic steatohepatitis (NASH). Although dysregulated lipid accumulation occurs across the spectrum of NAFLD, features of liver cell injury, such as hepatocyte ballooning, cytoskeletal changes (Mallory-Denk bodies), and hepatocyte apoptosis, occur predominantly in NASH and distinguish NASH from simple steatosis. Indeed, NASH is a more serious form of liver damage because cirrhosis and hepatocellular carcinoma are potential outcomes of NASH. Meanwhile, cirrhosis and hepatocellular carcinoma rarely occur in individuals with simple steatosis. Hepatic injury and apoptosis that occur in adults are often dysregulated and accompanied by the accumulation of immune cells, which produce cytokines and growth factors that drive chronic inflammation and may result in fibrosis. This article summarizes the process of apoptosis and roles of putative cytokines in progressive NAFLD.