The evaluation of the natural history of chronic hepatitis B virus (HBV) infection requires the precise definition of the various clinical conditions that can be encountered (i.e. inactive carrier state or subject with liver disease activity). This can be achieved by repeat monitoring of ALT, serum HBV-DNA levels (over a period of at least 1 year, according to international guidelines) and/or evaluation of HBsAg titre. Liver biopsy may offer additional information although it is not mandatory. Overall, the natural history of the true inactive carrier is benign: reactivation of hepatitis, especially in Western countries, is rare and is usually due to co-factors (like alcohol or drugs); spontaneous HBsAg loss is frequent (around 1% per year) and HCC development rare. On the other hand, in patients with chronic hepatitis B or cirrhosis, the risk of reactivation, of HCC development and of liver-related mortality is much higher, especially in Eastern countries, and should therefore lead to antiviral therapy.