Podocytes are the main gatekeeper of protein filtration in the glomerulus. When podocytes work less efficiently, this translates to the appearance of proteins in the urine, a condition that, if not promptly treated, leads to progression of glomerular damage and renal failure.Novel gene mutations have been uncovered in patients with nephrotic syndrome combined with a better definition of the role of podocin mutations. Although the importance of the inflammasome pathway and of the mechanisms of autophagy in podocyte health and disease have been increasingly recognized, a precise relationship between these processes still needs to be assessed. Numerous potential therapeutic targets have been identified and numerous data support the possibility of boosting podocyte regeneration. However, translation of experimental results into the clinic could largely depend on the avoidance of undesired side-effects; nanomedicine could provide the means to target old and novel drugs specifically to the podocytes.Podocytes are key cells in the glomerulus, and their damage inevitably leads to proteinuria and glomerular dysfunction. The more is known about the causes and mechanisms of podocyte damage, the more it will be possible to find new cures for glomerular diseases of the kidney.