Individual cells in their particular environments adhere to the extracellular matrix (ECM) and their neighbours via integrin-containing and cadherin-containing complexes, respectively. The dynamics of these interactions regulate the formation and maintenance of complex tissues. An expanding body of evidence accentuates the role of the small Rap1 GTPase and its associated signaling network in many of these processes. In this review we will discuss more recently revealed roles of Rap1 signaling by primarily focusing on functions of the Rap1 effectors RIAM, KRIT-1/CCM1 and AF-6/Afadin in junctional regulation of the vascular system and in epithelial cells. Furthermore, we will describe novel findings on the Rap activator PDZ-GEF in the regulation of cell–cell adhesion between epithelial cells and within a stem cell niche.