The optimal treatment of severe lupus nephritis remains unclear. Regimens consisting of steroid and cyclophosphamide (CYC) appear to be most effective. Infection and gonadal toxicity is a major concern of CYC use in patients of reproductive age. In addition, failure to respond or refractory to CYC treatment may lead to the development of end-stage renal disease. Mycophenolate mofetil (MMF) is a new immunosuppressive agent that selectively inhibits activated lymphocytes and renal mesangial cells. Data from experimental lupus nephritis and controlled studies, albeit small and lacking statistical power, have revealed that MMF is as effective in lupus patients as CYC in the induction of renal remission or as maintenance therapy to reduce renal flare in the short term. The significantly less ovarian toxicity and infection when compared to CYC are particularly attractive for the consideration of MMF in lupus nephritis. The potential of other new therapeutic agents is discussed together with the need for patient recruitment in future trials of lupus nephritis to address the importance of ethnicity as well as histological grading.