The viruses covered in the previous chapters all caused acute infection. In virological parlance, an acute infectious agent enters the host and the infection has only one of two outcomes. Either the infected individual mounts an effective immune response that allows them to recover and completely eliminate the virus from the body or they die. Unfortunately, many viruses are much more insidious and can cause persistent, chronic infections. For persistent viruses, after recovery from the initial infection, instead of being eliminated, these viruses circumvent the immune defenses and remain in the host indefinitely. Since these affected individuals are usually healthy and symptom-free, they are often unaware that they now have a permanent infection. For some viruses, the persistent virus is latent and lurks in the body with little or no replication although it may be triggered to reproduce months to years later. While the virus is latent these carriers have no symptoms and are not infectious. However, when reactivated, these latent viruses can give rise to acute disease again and can be spread to other individuals (see Chap. 10 —Chickenpox). In contrast to latent viruses, some persistent viruses are chronic and continue to reproduce in the afflicted individual even though there may be no obvious signs of disease. The continual production of new viruses makes these carriers infectious and a public health risk as they can unknowingly pass the virus on to unsuspecting contacts. In addition, some chronic viral infections slowly cause damage that accumulates and can lead to disease and death decades after the initial infection. Hepatitis B virus is one of the chronic viruses, and lifelong infections are associated with liver damage, including a high incidence of liver cirrhosis and liver cancer. The discovery of this virus and its conquest through vaccine development is a fascinating saga encompassing both triumphs and tragedies as well as introducing a new paradigm for viral vaccines, the subunit vaccine.