Steroid minimization has always been one of the most desired goals regarding immunosuppressive therapy after renal transplantation. Following the introduction of cyclosporine different steroid-free protocols became available, but their implementation was limited due to the high risk of acute rejection. In the last few years, the use of a very low dose of prednisone (5 mg/day) has been deemed to guarantee a good balance between steroid toxicity and efficacy. However, high interpatient variability in prednisolone exposure prevented the standard low dose to be as safe as expected in all patients. Therefore, steroid side effects can still be observed in a variable percentage of patients. In this setting, the personalization of steroid dosage might prevent an over exposure to the drug, but this strategy is not available yet. Thus, steroid withdrawal remains the only available strategy to limit side effects. In the last 40 years, we learned that steroid free protocols are associated with a higher risk of acute rejection, but they do not reduce graft survival. Hence, patients at higher risk for acute rejection or recurrence of their primary renal disease are usually excluded from these protocols. Early steroid withdrawal (within 7 days after transplantation) has been widely used and also suggested by American guidelines. However, steroid withdrawal 3-4 months after transplantation has been preferred by many Authors and deemed equally efficient. In addition, early but not late steroid withdrawal should always be associated to induction therapy. Lastly, Tacrolimus plus Mycophenolic Acid has become the most used association in steroid minimization protocols.