Despite the existence of Hepatitis B vaccination, hepatitis B virus (HBV) infection is still prevalent worldwide and accounts for significant morbidity and mortality. It is encouraging that majority of patients do recover from the acute infection, however, those that progress to chronic disease state is at great risk of developing complications such as hepatocellular carcinoma, cirrhosis and liver failure. Hepatitis B virus infection can be influenced by many factors such as host immune status, age at infection, and level of viral replication. The discovery about the existence of various genotypes and its association with different geographic distribution as well as the knowledge regarding mutant species has aid us in better understanding the nature of HBV infection and in delivering better care for patients. It is especially important to recognize those individuals with HBeAg-negative chronic HBV as they have a poorer prognosis compare with their counterparts, HBeAg-positive. Tremendous progress has been made over the years in understanding the behavior and clinical course of the disease; however, the natural history of HBV is complex and we still have much to explore and learn.