Nephrotic syndrome (NS) is a group of clinical symptoms resulting from massive proteinuria caused by impairment of the glomerular filtration barrier. The filtration barrier comprises glomerular basement membrane with endothelial cells lining its inner side and a podocyte monolayer covering its outer aspect. As well as forming part of the glomerular filter, podocytes also regulate synthesis of other components of the filtration barrier. Therefore, integrity of these cells is crucial for maintaining the normal ultrafiltration function. The pathogenesis of idiopathic nephrotic syndrome (INS) was proposed to be associated with autoimmunity and appearance in the circulation of a still unknown protein permeability factor (PF) inducing changes in the glomerular filtration barrier. Several candidate PFs have been identified to date, and current results indicate that podocytes are target cells for all of them. Changes in podocyte structure and functions induced by these factors are typical for changes observed in patients with nephrotic proteinuria. Most pharmacotherapeutic approaches in NS are based on various immunosuppressive agents and are targeted toward minimizing proteinuria. It appears, however, that these drugs not only target the cells of the immune system but also act directly on podocytes. Thus, it can be concluded that detailed studies on mechanisms regulating podocyte functions as well as designing drugs to protect these cells are required for effective therapy of NS.