The activation of complement contributes to tissue damage in many ways. Prevention of complement activation in organ transplantation has largely centred on studies in xenotransplantation, where complement plays a key role in the pathogenesis of hyperacute rejection. Transgenic porcine organs expressing human regulators of complement activation in combination with soluble inhibitors as well as appropriate immunosuppression may be sufficient to alleviate the major immunological barriers that currently prevent the use of xenogeneic organs for human transplantation.