Glomerular diseases are the leading causes of chronic and end-stage kidney disease. In the 1980s and 1990s, attention was focused on the biology and role of glomerular endothelial and mesangial cells. For the past two decades, seminal discoveries have been made in podocyte biology in health and disease. More recently, the glomerular parietal epithelial cell (PEC)-the fourth resident glomerular cell type-has been under active study, leading to a better understanding and definition of how these cells behave normally, and their potential roles in glomerular disease. Accordingly, this Review will focus on our current knowledge of PECs, in both health and disease. We discuss model systems to study PECs, how PECs might contribute to glomerulosclerosis, crescent and pseudocrescent formation and how PECs handle filtered albumin. These events have consequences on PEC structure and function, and PECs have potential roles as stem or progenitor cells for podocytes in glomerular regeneration, which will also be described.