The role of antibodies directed against Galα1-3Gal (α-Gal) epitopes in porcine-to-primate xenotransplantation has been widely studied during the past few years. These antibodies (anti-α-Gal) have been associated with both hyperacute rejection and acute vascular rejection of vascularized organs. Depletion and (temporary or permanent) suppression of production of anti-α- Gal seem to be essential to the long-term survival of these organs, even when the ultimate aim is accommodation or tolerance. Although more than 95% depletion of anti-α-Gal can be achieved by the use of immunoaffinity column technology, to date no regimen has been successful in preventing the return of anti-α-Gal (from continuing production). In this review, we discuss current and novel methods for achieving depletion or inhibition (i.e. extracorporeal immunoadsorption, anti-idiotypic antibodies, the intravenous infusion of immunoglobulin or oligosaccharides) and suppression of production (i.e. irradiation, pharmacologic agents, specific monoclonal antibodies, immunotoxins) of anti-α-Gal antibodies.