Patients with chronic hepatitis B virus infection are at increased risk for the development of cirrhosis and hepatocellular carcinoma. Viral suppression with antiviral therapy has been shown to decrease the risk of these complications. Criteria for initiation of antiviral therapy have evolved over time to include serum alanine aminotransferase elevation, serum hepatitis B virus DNA elevations, and histologic assessment. Current societal guidelines and a treatment algorithm have been developed to guide decision-making as regards to antiviral therapy. More recent data has shown the importance of basal core/core promoter mutations, serum albumin, and platelet count in predicting complications of chronic hepatitis B. We present a new treatment strategy for determining the need for antiviral therapy in patients with chronic hepatitis B.