Glomerulonephritis remains the second or third most common primary renal disease type to progress to end-stage renal failure. This disease type is particularly important because its focus is limited to the kidney and its reversal or stabilization ensures a return to a normal quality of life for the individual. Also, because its highest incidence rate is in childhood and early adulthood, the implications of effective therapy in terms of preventing end-stage renal failure costs, benefits not only the individual but also society. We focus on the 3 most common variants that progress to end-stage renal failure (ie, membranous nephropathy [MGN], focal segmental glomerulosclerosis [FSGS], and IgA nephropathy). Together these represent approximately 80% of the primary glomerular diseases known to progress. We discuss the outcome studies published over the past decade in these disorders that permit the best insight into specific immunotherapy. We provide this data in an evidence-based model so the reader can appreciate the strengths and/or weaknesses of the therapies discussed and we provide a framework for clinical management.