Two major hurdles remain before xenotransplantation can enter the clinic. The first is the more technical issue of being able to overcome the human immune response that leads to rejection of transplanted organs/cells from other species. The second, reviewed here, concerns the potential risk of inadvertent transfer of animal viruses present in the xenotransplant that are able to infect the human recipient. The threat from viruses is a particularly contentious topic because it poses a risk not only to those individuals who receive xenotransplants, but also to healthy individuals who come into contact, either directly or indirectly, with the xenotransplant recipient. In this review, we describe some of the virus types, in addition to the much discussed porcine endogenous retroviruses that might cross the species barrier, and assess the risk of such viruses causing disease in human hosts.