Amongst all human pathogens, the hepatitis B virus is one of the smallest known. The virus particle itself was first described in this Medical School nearly 40 years ago, although its existence had been surmised for much longer. Not only is the virus small in physical size, its genetic information is tiny, one thousandth of that in an average bacterium. It has a fascinatingly complex lifestyle that continues to yield insights into host parasite relationships and the way in which persistent infections by some viruses have evolved to confuse the immune system. This poses problems for vaccines and for antiviral drug therapy, a conundrum now far more intricate than ever imagined.