Summary. Integrins are cell surface adhesion and signaling receptors important for cell adhesion, survival and migration. Integrins are known to be regulated by signals from inside the cells. Such inside-out regulation modulates affinities of integrins for their extracellular matrix ligand and is critical for thrombosis, haemostasis and immune response. Talin and kindlin, two integrin binding proteins, have been shown to be important regulators of integrin function. In this review, we will focus on the molecular mechanism of integrin regulation that has emerged from recent structural, biochemical and genetic studies.