Currently, the number of patients awaiting transplantation is continuously increasing, and shortage of available deceased organ donors is the major limitation for organ and cell allotransplantation. Research to develop alternative sources of tissues is ongoing and xenogeneic organs or cells represent an attractive solution. This review focuses on recent progress achieved in this field, including the development of newly genetically modified animal donors and new immunosuppressive approaches. As xenotransplantation is moving closer to clinical application, future perspectives must establish guidelines to ensure that future clinical trials are carried out ethically and safely.