Focal segmental glomerulosclerosis (FSGS) remains an enigmatic disease despite many years of study. There has been a recent increased incidence of FSGS particularly in African Americans in whom the outcome tends to be worse. In about 30% of patients transplanted for FSGS, the disease recurs and often results in severe nephrotic syndrome and accelerated graft loss. FSGS is a common cause of nephrotic disease accounting for 10-20% of cases of idiopathic nephrotic syndrome in children and 35% of cases in adults. Most cases are refractory to current therapy resulting in the ultimate progression to end stage renal disease. Overall, FSGS accounts for about 15% of pediatric and 5% of adult cases of end stage renal disease. With the frequent post transplant recurrence, the morbidity and mortality of FSGS is increased. Thus, FSGS is a disease that is associated with a large cost to society and long-term morbidity to the individual patient. A treatment that could induce permanent remission and reverse organ damage would make a major contribution to society by reduction of these expenses. A circulating Permeability Factor (PF, Savin Factor) has been suspected as central to the pathogenesis of recurrent disease but its identity has been difficult to discern. The molecular weight has reported to be between 30 and 100 kDa. Although, PF has been reported to adhere to protein A columns and such columns can be part of the treatment of FSGS, this molecular weight would exclude PF being an intact antibody. Immunosuppressive agents have been the only therapy demonstrating efficacy, albeit partial, suggesting that at least some cases of FSGS are immune mediated. While high dose steroids are the first line of treatment for FSGS, cyclosporine has been efficacious in randomized trials and has been used for steroid resistant FSGS but is associated with substantial toxicity. If cyclosporine fails, cyclophosphamide, plasmapheresis, protein A immunoabsorption, and most recently mycophenolate mofetil (MMF) have been used with variable efficacy.