Focal segmental glomerulosclerosis (FSGS) is a clinicopathologic syndrome with a substantial risk for progression to end-stage renal disease (ESRD). Recent studies of renal biopsy archives in the United States suggest that the incidence of FSGS has increased. FSGS has become the leading cause of idiopathic nephrotic syndrome in the United States, with the greatest incidence rates in the black population. In the absence of a population-based estimate of FSGS incidence, we wished to obtain a population-based estimate of incident ESRD cases caused by FSGS (FSGS ESRD) and characterize temporal changes in this group. We examined the incidence of FSGS ESRD during a 21-year period (1980 to 2000) using data from the United States Renal Data System. We excluded patients who were classified as having acquired immunodeficiency syndrome nephropathy. The annual incidence of FSGS ESRD has increased considerably, whether expressed as an absolute number or a fraction of the total incident ESRD population. Thus, the proportion of ESRD attributed to FSGS has increased 11-fold, from 0.2% in 1980 to 2.3% in 2000. The recent increase in incident FSGS ESRD cases likely is multifactorial in origin, with contributions from changes in renal biopsy practices, changes in disease classification, and a real increase in the incidence of FSGS disease. Black individuals have a 4-fold greater risk of FSGS ESRD than white or Asian individuals. The peak decade for FSGS ESRD incidence is 40 to 49 years among black subjects and 70 to 79 years among white and Asian individuals. Males have 1.5- to 2-fold greater risk than females. The incidence of FSGS ESRD has increased considerably in the United States, with black individuals at greatest risk. Idiopathic FSGS now is the most common cause of ESRD caused by primary glomerular disease in the United States in both the black and white populations.