Why do viruses cause disease? As intracellular parasites they grow at the expense of the host, yet many infections are non-virulent. We tend to focus on unusual outcomes of infection that are important to the individual but trivial for host–parasite evolution, for example, paralytic polio or viral cancer. The assumption that the features of disease help onward transmission of the virus is true for, say, rabies, but not for AIDS or neurodegenerative diseases. Moreover, minor host differences can result in major changes in pathogen virulence. Although viral burden relates to disease severity, pathogenesis is not necessarily coupled with transmission dynamics.