Highly sensitized patients (anti-HLA) on the kidney waiting list wait longer for a suitable crossmatch negative organ. At the moment there are two strategies to enhance transplantation of these patients. One approach is the determination of acceptable HLA mismatches and application of this knowledge for the selection of crossmatch negative donors, and the second is the desensitization of patients with intravenous immunoglobulin-based protocols to enable transplantation of an organ from a donor towards which antibodies were originally present. Both approaches have advantages and disadvantages and are only successful in a proportion of the patients. The optimal solution is an integrated strategy whereby desensitization is used for those patients for whom the acceptable mismatch approach is not successful.