The optimum therapy for patients with lupus nephritis is a hotly debated topic. Prospective randomized studies in patients with proliferative lupus nephritis have established the superiority of cyclophosphamide to azathioprine, both of which are used in combination with corticosteroids. Although high-dose, intermittent administration of cyclophosphamide (pulse therapy) has significantly reduced the toxicity associated with this drug, premature ovarian failure and infections remain considerable problems. Short-term to intermediate-term, randomized controlled trials have shown that mycophenolate mofetil is a good option for the induction and maintenance of remission in lupus nephritis patients. Additional longer-term trials involving more patients and stricter outcomes based on renal function are needed, however, before claims that mycophenolate mofetil is superior to cyclophosphamide can be substantiated. Until such data are available, physicians caring for patients with lupus nephritis can use mycophenolate mofetil as induction or maintenance therapy for selected patients under close observation. Small noncontrolled trials with short-term follow-up suggest that up to 50% of patients who are refractory to cyclophosphamide might have a clinically significant response to rituximab, a monoclonal antibody directed against B cells.