Recent advances have identified the podocyte as a key target in glomerular injury. The podocyte is a highly specialized cell which is responsible for the glomerular permselectivity for proteins in the kidney. Podocyte injury or loss leads to proteinuria. Apoptosis has been shown to contribute to renal cell loss, including loss of podocytes. The most striking feature of the podocyte is its ability to form intricate specialized cell junctions, the slit diaphragm. Slit diaphragm proteins play an important role in podocyte biology, protein permselectivity, cell signalling and disease. This review focuses on recent advances on the understanding of podocyte survival regulation, its relationship to slit diaphragm structure and function, and how this knowledge may affect our therapeutic approach to proteinuric kidney disease.