Cell-matrix adhesion is crucial for maintaining the mechanical integrity of epithelial tissues. Podocytes--a key component of the glomerular filtration barrier--are exposed to permanent transcapillary filtration pressure and must therefore adhere tightly to the underlying glomerular basement membrane (GBM). The major cell-matrix adhesion receptor in podocytes is the integrin α3β1, which connects laminin 521 in the GBM through various adaptor proteins to the intracellular actin cytoskeleton. Other cell-matrix adhesion receptors expressed by podocytes include the integrins α2β1 and αvβ3, α-dystroglycan, syndecan-4 and type XVII collagen. Mutations in genes encoding any of the components critical for podocyte adhesion cause glomerular disease. This Review highlights recent advances in our understanding of the cell biology and genetics of podocyte adhesion with special emphasis on glomerular disease.