Leukocyte transendothelial migration (TEM) requires endothelial signalling. This signalling is initiated by clustering of cell-surface adhesion molecules and transmitted into the endothelium by a group of associated or co-clustered adapter proteins. These adapter proteins, such as cortactin and filamin, connect the adhesion molecules to the actin cytoskeleton as well as to signalling enzymes and downstream pathways. This short review aims to define common themes in adapter protein binding in endothelial cells and to propose critical functions that are exerted by these adapters in leukocyte transendothelial migration.