1. Xenotransplantation, or transplantation across species, leads to rejection, which destroys the xenograft within hours to days of transplantation. 2. Complement is a major barrier to xenotransplantation of vascularized organs and is believed to play an important role in the rejection process. 3. The present paper reviews three aspects of complement in xenotransplantation. These include the mechanisms and regulation of complement activation as well as tissue injury mediated by complement activation.