Cell surface proteins which mediate tolerance or rejection of transplanted organs have been well characterized in people. However, despite the relative conservation of the acquired immune response in mammals, for unknown reasons dogs and cats either tolerate transplanted organs more readily or reject them more vigorously. The rejection-associated histologic changes found in human and animal grafts imply that the immune response to graft proteins is not identical amongst species. As a result few tissues or organs are routinely transplanted in client-owned dogs and cats, and larger studies are still needed to characterize chronic changes that may develop. With the continual development of new immunosuppressive drugs and refinement of existing protocols, transplantation options will hopefully increase via the use of xenograft tissues, particularly in dogs.