Proliferative lupus nephritis is the most severe form of lupus nephritis. Outcomes of this disease are affected by ethnicity, clinical characteristics, irreversible damage on renal biopsy, initial response to treatment and future disease course (for example, the occurrence of renal flares). Initial intensive (induction) treatment of proliferative lupus nephritis is aimed at achieving remission, but optimal duration and intensity are not well defined. A combination of intravenous cyclophosphamide and corticosteroids have been shown to decrease the risk of end-stage renal disease, but are associated with substantial acute toxic effects (such as infections) and chronic toxic effects (such as ovarian failure). In white populations, low-dose cyclophosphamide is a reasonable alternative to high-dose cyclophosphamide as it is similarly effective and associated with less toxicity. Mycophenolate mofetil is as effective as high-dose intravenous cyclophosphamide in terms of inducing remission and similar in terms of safety. Although most patients respond to induction treatment, remission is often only achieved after patients are switched to maintenance treatment. As maintenance treatment, mycophenolate mofetil is superior to azathioprine and azathioprine is similarly effective to ciclosporin in terms of prevention or reducing the risk of relapse. Rituximab should be reserved for patients with refractory disease. Treatment of lupus nephritis should be individually tailored to patients, with more aggressive therapy reserved for patients at high risk of renal dysfunction and progression of renal disease.