Kidney transplantation is considered the best treatment for patients with end-stage renal failure, even in extreme age-groups. Immunosuppression for "life" is, however, mandatory. This chronic, somewhat unselected, inhibition of the host immune system may induce complications, such as cancer and infection, that could counterbalance the benefits achieved by the transplant. In addition, all currently used immunosuppressors have several side-effects, impeding their long-term use. Consequently, drug associations are frequently tested by different centres according to their own practices, resulting in different survival and tolerance profiles. Corticosteroids and calcineurin inhibitors are the cornerstones of current immunosuppressive regimens. However, they are also the main culprits of adverse-events and side-effects encountered after transplantation. Lowering the doses of each drug, or even eliminating them from the immunosuppressive menu, has been evaluated by many groups over the last two decades. This review summarises a huge number of studies dealing with corticosteroid and calcineurin inhibitor minimization, including withdrawal and avoidance trials. It is hard today to propose any practical guidelines on such a controversial topic. Good results are achieved by some groups and bad results by others. The lack of long-term follow-up in randomized studies contributes to this debate. Nevertheless, it seems possible and safe to avoid corticosteroids and/or calcineurin inhibitors in many patients. The application of protocol biopsies as well as new immunological tests to determine the degree of immunosuppression will certainly help transplant physicians to provide more personalized treatment strategies.