Cell-cell adhesion plays a fundamental role in cell polarity and organogenesis. It also contributes to the formation and establishment of physical barriers against microbial infections. However, a large number of pathogens, from viruses to bacteria and parasites, have developed countless strategies to specifically target cell adhesion molecules in order to adhere to and invade epithelial cells, disrupt epithelial integrity, and access deeper tissues for dissemination. The study of all these processes has contributed to the characterization of molecular machineries at the junctions of eukaryotic cells that have been better understood by using pathogens as probes.