Xenotransplantation is a potential solution to the current donor shortage for allotransplantation. Likewise it is being investigated for a number of other disease states such as Parkinson's disease, diabetes, and acquired immunodeficiency disease. Infections are a concern with the use of any biologic agent and as such have proved to be a substantial cause of morbidity and mortality after allotransplantation. Similarly, infections will likely cause disease after xenotransplantation. Public debate on the ethics of whether the field of xenotransplantation should move forward has focused on the concern of novel infections, xenozoonoses. Accordingly, the role of animal microbes must be critically examined. This article reviews mechanisms for xenogeneic infections and details what is known and what still needs to be learned as the field of xenotransplantation progresses. Emphasis is placed on microbial agents of baboons and swine, as they are currently the most common species considered as donor sources for xenotransplantation.