Organ branching morphogenesis is a complex process that requires many coordinated cell functions, including cell migration, proliferation, and polarization. This process is regulated at numerous levels, including spatial and temporal expression of transcription factors and their regulators; growth factors and their receptors; as well as cell–cell and cell–extracellular matrix interactions. Integrins and dystroglycan are transmembrane receptors that control both the adhesion of cells to matrix components as well as transduction of signaling coming from and directed to the matrix. In this article we review current advances defining the roles of these receptors in branching morphogenesis focusing on the major epithelial cell derived structures in mammals, namely salivary gland, mammary gland, lung, pancreas, and kidney.