The polysaccharide heparan sulphate is ubiquitously expressed as a proteoglycan in extracellular matrices and on cell surfaces. Heparan sulphate has marked sequence diversity that allows it to specifically interact with many proteins. This Review focuses on the multiple roles of heparan sulphate in inflammatory responses and, in particular, on its participation in almost every stage of leukocyte transmigration through the blood-vessel wall. Heparan sulphate is involved in the initial adhesion of leukocytes to the inflamed endothelium, the subsequent chemokine-mediated transmigration through the vessel wall and the establishment of both acute and chronic inflammatory reactions.