Post-transplantation infections are common in allograft recipients and should be expected in all immunocompromised hosts. Based on the need for immunosuppression in xenotransplantation, procedures developed to enhance safety in allotransplantation can be applied in future xenotransplantation clinical trials. Standardized approaches can be developed to guide the evaluation of common infectious syndromes in xenograft recipients. The opportunity created by screening of swine intended as xenograft donors has equal applicability to allotransplantation—notably broader screening strategies for allograft donors such as use of advanced sequencing modalities including broad-range molecular probes, microarrays, and high-throughput pyrosequencing. Considerations in management of allotransplant- and xenotransplant-associated infections are largely the same. Experience in xenotransplantation will continue to inform thinking regarding donor-derived infections in allotransplantation. We expect that experience in managing complex allotransplant recipients will similarly inform clinical trials in xenotransplantation.