Transfusion and other medical interventions, as well as their non-medical derivatives, have a lot to answer for. Much of HCV infection can be traced back to this route, HGV is still being transmitted in this way and a substantial proportion of HBV in Africa has been spread around by use of contaminated skin-piercing manoeuvres, medical or otherwise. Many practitioners can still remember the days when blood-borne viruses were not a major feature of medical curricula. Unfortunately, patients currently subjected to cost-cutting medical practices, for example use of unscreened blood and re-use of needles, will have to pay the price in years to come. The evolution of these viruses is linked to their route of introduction, but the relationship between variability and clinical outcome is less certain. Nevertheless, variability is important for clinical practice, especially for the design of sensitive diagnostics and highly effective vaccines.