Systemic lupus erythematosus, which predominantly affects young women, is frequently complicated by renal involvement. The presence of acute glomerulonephritis significantly adds to morbidity and mortality. Cyclophosphamide has become the mainstay of treatment in patients with proliferative forms of lupus nephritis. However, adverse events such as severe infections and infertility have spurred the search for novel treatment regimens and agents. Sequential therapy has significantly reduced adverse events. In several pilot studies, mycophenolate mofetil (MMF) has emerged as a promising therapeutic approach for both the induction and maintenance phase in patients with lupus nephritis, delivering equal efficacy and a better adverse effect profile; however, these studies had a limited power, and a large, multicentre and probably multinational clinical trial will be needed to discern the optimal therapeutic approach. On the basis of the currently available literature, sequential therapy with cyclophosphamide induction followed by azathioprine or MMF maintenance can be recommended for most patients. In selected populations, induction with MMF is a reasonable option to reduce adverse events.