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Immunosuppressive therapy is a key component for successful kidney transplantation. It is commonly believed that more intensive immunosuppression is needed initially to prevent rejection episodes and less immunosuppression is subsequently maintained to minimize the overall risk of infection and malignancy. The selection of drugs should be guided by a comprehensive assessment of the immunologic risk, patient comorbidities, financial cost, drug efficacy and adverse effects. Lymphocyte-depleting antibody induction is recommended for patients with high immunologic risk, while IL-2R antibody can be used for low or moderate risk patients. Patients with very low risk may be induced with intravenous steroids without using an antibody. A maintenance regimen typically consists of a low-dose of steroid combined with two of the four class drugs: calcineurin inhibitor (tacrolimus or cyclosporine), antimetabolite (mycophenolate mofetil or enteric coated mycophenolate sodium), mTOR inhibitor (sirolimus or everolimus) and costimulation blocker (belatacept). Currently in the USA, the most popular maintenance is the combination of corticosteroid, mycophenolic acid and tacrolimus. Steroid minimization, or calcineurin inhibitor free or withdrawal should be limited to the highly selected patients with low immunological risk. Recently, the novel biological agent belatacept-based maintenance has demonstrated a significantly better renal function and improved cardiovascular and metabolic profile, which may provide hope for an ultimate survival benefit.