Infectious risk remains an important consideration in the clinical application of xenotransplantation. Vascularized xenografts create unique immunological niches in which bidirectional transmission of pathogens between donor and recipient may occur. Enhanced replication of many pathogens is stimulated by the immune responses induced by transplantation and by the immune suppression used to prevent graft rejection. Herpesviruses are the prototype viruses that are activated during immunosuppression. Quantitative diagnostic molecular assays have been developed for the known herpesviruses causing infection in pigs. Recent data suggest that some herpesviral infections, such as porcine cytomegalovirus, may be excluded from swine used as source animals by careful breeding, while others will require novel strategies for control. This review focuses on porcine and baboon herpesviruses in pig-to-non-human primate solid organ xenotransplantation including direct effects (tissue damage), indirect effects (coagulopathy, rejection), and possible approaches to these infections.