Despite the availability of an efficient hepatitis B vaccine, approximately 240 million individuals are chronically infected with hepatitis B virus worldwide. One-fourth of hepatitis B surface antigen (HBsAg)-positive patients will develop complications, such as cirrhosis or hepatocellular carcinoma, both major causes of liver-related deaths. Antiviral therapies, such as pegylated interferon alpha or nucleoside/nucleotide analogues, are effective in suppressing HBV DNA and reducing the subsequent risk of fibrosis progression, cirrhosis and hepatocellular carcinoma. HBsAg has proven to be a steady, reliable marker of chronic HBV carriage that can also be used to predict clinical outcomes. Three commercial enzyme immunoassays are now available for HBsAg quantification. A number of recent studies have shown clinical utility of HBsAg quantification in combination with HBV DNA levels to identify inactive carriers who need antiviral therapy and in interferon treated-patients in order to predict the virological response to pegylated interferon alpha.