Directionalmigrationofleukocytesisindispensabletoinnateimmunityforhostdefense.However,recruitmentofleukocytestoasiteoftissueinjuryalsoconstitutesaleadingcauseforinflammatoryresponses.Mechanistically,itinvolvesacascadeofcellulareventspreciselyregulatedbytemporalandspatialpresentationofarepertoireofmoleculesinthemigratingleukocytesandtheirsurroundings(microenvironments).HereIwillsummarizetheemergingevidencethathasshedlightsontheunderlyingmolecularmechanismfordirectionalmigrationofleukocytes,whichhasguidedthetherapeuticaldevelopmentforinnovativeanti-inflammatorymedicines.