Tolerance to allografts would mean a better quality of life and prognosis for transplant patients. Despite the first descriptions of tolerance to alloantigens over 50 years ago, deliberately induced tolerance in the clinic on a wide scale remains a goal that is not quite in reach. However, much progress has been made in understanding tolerance in rodent models and in the few reports of induced or spontaneously occurring tolerance in humans. Here, we review this progress made in the quest to achieve clinical tolerance.