Almost all mammalian cell types have morphologies that are uniquely tailored to their physiological functions. This immense variation in cell shape depends on an underlying network of dynamic and interconnected actin and microtubule polymers. The glomerular podocyte is an archetypal example of such specialization, with a complex cytoskeleton underlying its delicate architectural features. Dynamic control of this cytoskeletal matrix seems to center around the slit diaphragm, a complex of proteins at the cell–cell junction between adjacent podocyte foot processes. This junction includes molecules that are unique to the podocyte that probably determine the correct morphology of the cell, and are targets of disease processes that disrupt the intricate balance of signaling that controls the cytoskeletal matrix. This Review will outline the most recent concepts and advances in our understanding of this critical aspect of glomerular biology, as well as discussing how an improved understanding of the podocyte cytoskeleton is starting to shape advances in delineating the pathogenesis of common glomerular diseases.