The molecular regulation of the specific sets of endothelial receptors that mediate leukocyte diapedesis is not fully understood. Using elegant adoptive transfer experiments with cells from genetically deficient mouse models, in this issue of Blood Woodfin and colleagues show that the junctional molecules ICAM-2, JAM-A, and PECAM-1 mediate neutrophil transmigration in a stimulus-dependent manner and define how this ability is regulated by the activated endothelium.