Liver transplantation has become the treatment of choice for patients with end-stage liver disease. De novo hepatitis B infection after liver transplantation is a rare event and usually runs a mild clinical and histological course. Despite the favourable outcome, a wide spectrum of hepatitis B virus (HBV)-associated liver disease may develop, ranging from asymptomatic carriage to severe chronic active hepatitis or cirrhosis and even fulminant hepatic failure. The achievement of protective titres of anti-HBs through vaccination has been suggested to be protective against the development of de novo HBV infection. The results of vaccination in cirrhotic patients awaiting for liver transplant have been very disappointing. High-dose/short-term schedules have been tried in transplant candidates in order to increase the response rate. New and more immunogenic formulations (containing new adjuvants or additional pre-S1/pre-S2 recombinant antigens), and, more importantly, early vaccination of potential transplant candidates at earlier stages of their liver disease should further prevent de novo hepatitis B in transplant recipients.