Studies in non‐human primates to evaluate tolerance strategies in organ transplantation have led to innovation in human transplantation. The two strategies we have studied in detail in non‐human primates are T‐cell depletion by anti‐CD3 immunotoxin and co‐stimulation blockade. Each of these strategies has been extended into early human trials in renal transplantation. The results of these human and non‐human primate studies are summarized. Continued progress in better and safer immunosuppressive methods remains closely linked to research using non‐human primates. However, there has not been a one‐to‐one correspondence between efficacy in the primate and efficacy in humans. Rather, principles can be derived from non‐human primate studies that can be extended into human trials with the knowledge that regimens will likely differ in humans compared to non‐human primates.