Integrin cell-adhesion receptors mediate interactions between cells and the extracellular matrix. Dynamic regulation of integrin adhesive function is termed 'activation' or 'inside-out' signalling. Activation is key to integrin function in processes as diverse as cell migration, the organization of the extracellular matrix and platelet aggregation. Consequently, there has been an intense effort to elucidate the molecular mechanism of integrin activation. This has resulted in the recent identification of novel cytoplasmic partners for integrins and the emerging characterization of the signal-transduction pathways that regulate integrin 'inside-out' signalling. Here, the authors review the recent developments that have provided us with an increased understanding of the basis of integrin activation.