The coordinate modulation of the cellular functions of cadherins and integrins plays an essential role in fundamental physiological and pathological processes, including morphogenesis, tissue differentiation and renewal, wound healing, immune surveillance, inflammatory response, tumour progression, and metastasis. However, the molecular mechanisms underlying the fine-balanced relationship between cadherin and integrin functions are still elusive. This review focuses on recent findings on the involvement of the small GTPase Rap1 in the regulation of cadherin- and integrin-dependent cell adhesion and signal transduction. In particular, it highlights some of the novel results recently obtained that raise the possibility of a pivotal role for Rap1 in the functional crosstalk between cadherins and integrins, suggesting interesting new regulatory mechanisms.