Treatment of proliferative lupus nephritis (PLN) consists of an initial aggressive treatment aimed to quench the hectic activity of the disease (induction phase) followed by a milder therapy aimed to prevent flares (maintenance treatment). There are a number of possible options for induction treatment. Intravenous (i.v.) pulses of cyclophosphamide plus oral or i.v. steroids is very effective but can be accompanied by severe adverse events. Alternatively, i.v. pulses of methylprednisolone (MPP) followed by a 2-3-month course of oral cyclophosphamide, or mycophenolate mofetil (MMF) plus prednisone, seem to be as effective as i.v. cyclophosphamide and may be better tolerated. In cases refractory to these treatments, rituximab has been used successfully. However, the exact role of rituximab is difficult to ascertain as in most cases the drug was administered together with glucocorticoids or cyclophosphamide. Intravenous cyclophosphamide has also been prescribed for maintenance therapy with good results. However, recent trials showed that similar or even better results can be obtained with azathioprine or MMF associated with moderate doses of prednisone. Also cyclosporine can achieve good results while sparing steroids, particularly in patients with persistently elevated proteinuria. In summary, modern immunosuppression today allows us to reduce the dosage of steroids and to avoid the prolonged use of cyclophosphamide. These newer strategies may result in fewer adverse effects, better quality of life and better survival for patients with proliferative lupus nephritis.