Glomerulonephritis is a significant factor fueling the rapid increase in the population of patients with end-stage renal disease. Novel therapeutic strategies targeting specific mechanisms of glomerular destruction are the most reasonable approaches to arrest ongoing injury. In this review, we summarize some of our results obtained in our effort to characterize the role of 15-lipoxygenase activation as one of the mechansisms operative during the early, prefibrotic stage of glomerular immune injury. We also summarize the effects of cytokines released during these processes, as well as the activation by aspirin of the synthesis of 15-R-HETE (see text). Finally, we will propose a clinical approach to this group of disorders, based on emerging concepts of the pathophysiology of glomerulonephritis from our work and that of several other investigators.