The glomerulus of the mammalian kidney is an intricate structure that contains an unusual filtration barrier that retains higher molecular weight proteins and blood cells in the circulation. Recent studies have changed our conception of the glomerulus from a relatively static structure to a dynamic one, whose integrity depends on signaling between the three major cell lineages: podocytes, endothelial and mesangial cells. Research into the signaling pathways that control glomerular development and then maintain glomerular integrity and function has recently identified several genes, such as the nephrin and Wilms' tumor 1 genes, that are mutated in human kidney disease.