The principle that the induction of (mixed) hematopoietic chimerism can lead to transplantation tolerance to another organ from the same donor has been verified in rodents, in large animals including non-human primates and recently in a selected group of renal transplant recipients. The wide application of this tool depends on the development of more gentle, non-toxic induction protocols and reliable assays with which to detect the establishment of stable donor-specific tolerance.