The current shortage in human organs has made xenotransplantation a potential source of organ transplant in humans. Xenotransplantation attracted interest from regulatory authorities, particularly after the demonstration of pig-to-human transmission of porcine endogenous retrovirus (1996). This added to the risk of a product, resulting in a Guidance of the US Food and Drug Administration (2003). The European Medicines Agency issued a Guideline on xenogeneic cell therapy products (2009). These addressees the full flow chart starting with the designated pathogen free status of the source animal and special aspects regarding preclinical safety and monitoring toxicity, also archiving of records from the donor and recipient as well as storage of the sample. This article presents an overview of the regulatory framework with the special focus on the preclinical study regulation in US and Europe.