Background: Recent improvements in simultaneous pancreas-kidney transplantation (SPK) and the striking decrease in acute rejection lead us to focus on the effects of long-term immunosuppression. Aim of this study: Evaluation of a policy of steroid withdrawal and tailored immunosuppression in pancreas-kidney patients treated in a single center. Methods: review of the clinical charts in 9 SPK recipients (male/female = 5/4, median age 41 years, median follow-up 42 months), by the same operator, under supervision of the two usual caregivers. Therapeutic protocols. Induction phase: all patients received mycophenolate mophetil (starting dose: 2 grams), tacrolimus and steroids, 8 received Simulect, 1 received thymoglobulins. Maintenance therapy was slowly reduced, with the goal of steroid withdrawal. Results: The therapeutic adjustments were mainly determined by two almost opposing elements: 1. Rapid adjustments in the case of side-effects (gastrointestinal problems, infections and neoplasia); 2. Slow tapering off in the case of good organ function. On the other hand, a switch to cyclosporine A and to rapamycine was considered in the case of chronic organ malfunction. By these means, over a median of 42 months follow-up, steroid withdrawal was slowly obtained in 6/9 patients (at a median time of 25 months). Conclusion: Within the limits of this smallscale study, a tailored immunosuppressive policy allows at least some “positively selected” patients to reach the “dream” of steroid withdrawal after SPK.