The immune response against alloantigens involves the production of antibodies and development of T-cell immunity. Recipients sensitized to HLA antigens may have antibodies to almost all donors and may not be able to find a suitable kidney transplant donor. Strategies available to enable these patients to obtain a transplant are to give priority to highly sensitized patients, to perform therapy for antibody reduction or to transplant with existing antibodies and to intervene as needed with post-transplant treatment. While sensitization against HLA antigens is the most important cause of immunological transplant failure, other types of alloantigens, many of them expressed selectively in endothelial cells, and autoantigens may also be involved. Molecular typing and solid-phase antibody testing have markedly changed this field in the last few years. Methods for the analysis of HLA antibodies and for the study of T-cell reactivity and sensitization will also be discussed. Virtual cross-matching can now be performed for many patients, resulting in considerable savings in time and effort. Successful application of this approach requires the intervention of highly trained personnel with a good understanding of the limitations of the procedure and with intimate knowledge of the antibody profiles of the patients on the waiting list.