The Viral Hepatitis Prevention Board (VHPB) organized an international meeting in Milan in November 2011 on the question of whether completing a course of hepatitis B vaccination confers lifelong protection against hepatitis B virus infection and its complications. Presentations covered vaccine efficacy including factors influencing long-term protection; breakthrough infections; the immunological effect of natural boosting; the effectiveness of universal hepatitis B vaccination in different countries, and issues relating to national, regional and global policies on booster vaccination. Findings from four continents were presented at the meeting, with data now extending to follow-up for nearly 30 years after full primary vaccination. The results reported add to the extensive and growing body of knowledge, demonstrating that in spite of subsequent decline and ultimate loss of detectable serum anti-HBs, a full primary course of hepatitis B vaccine confers complete protection against acute clinical disease and chronic hepatitis B infection for long periods of time. Our understanding of the role and functions of T and B cells in protective immunity deepens, although the picture is still complex. A framework for future work in several areas emerged from the meeting, including monitoring and surveillance of vaccination programmes, breakthrough infections, hepatitis B in immigrant populations, and vaccine-escape viral mutants. One further concrete recommendation is the setting up of a working group to standardize definitions on terms such as “immunity”, “protection”, “immune memory”, “non-responders”, “long-term”, “anamnestic response”, “breakthrough” and “vaccine failure”.