Cells are exquisitely sensitive to the mechanical nature of their environment, including applied force and the stiffness of the extracellular matrix (ECM). Recent evidence has shown that these variables are critical regulators of diverse processes mediating embryonic development, adult tissue physiology, and many disease states, including cancer, atherosclerosis, and myopathies. Often, detection of mechanical stimuli is mediated by the structures that link cells that surround ECM, the focal adhesions (FAs). FAs are intrinsically force sensitive and display altered dynamics, structure, and composition in response to applied load. While much progress has been made in determining the proteins that localize to and regulate the formation of these structures, less is known about the role of tension across specific proteins in this process. A recently developed class of force-sensitive biosensors is enabling a greater understanding of the molecular bases of cellular mechanosensitivity and cell migration.