Corticosteroids and cytotoxic agents have been largely used in idiopathic membranous nephropathy (MN). A meta-analysis of controlled studies with corticosteroids did not demonstrate any benefit in using these agents on disease outcome. On the contrary, some controlled trials reported that cytotoxic agents can significantly reduce proteinuria. Three multicenter randomized controlled studies demonstrated that a regimen based on a 6-month treatment alternating every other month methylprednisolone with chlorambucil or cyclophosphamide, not only favors nephrotic syndrome remission, but can also protect long-term renal function. Cyclosporine has also been shown to be effective in inducing a partial or the complete remission of nephrotic syndrome. The main problem with cyclosporine is that in many responders proteinuria relapses when the drug is stopped. However, if the drug is given for a prolonged period and is tapered off gradually the risk of relapse can be reduced. A recent study showed that treatment with a long acting ACTH preparation for 1 yr was associated with significant long-term improvements in serum lipoprotein patterns, urinary protein excretion and glomerular function. Unfortunately, the study was not randomized, the number of patients was small and the follow-up was short. Advances in understanding the pathogenetic mechanisms of glomerulonephritis produced specifically new approaches to selected cell types or molecular pathways involved in MN pathogenesis. These therapies should guarantee therapeutic efficacy while limiting the adverse effects of non-selective immunosuppression. However, we need randomized clinical trials to ascertain how well they perform in practice rather than just on a theoretical basis.