The glycosaminoglycans (GAGs) heparan sulfate, dermatan sulfate and heparin are important anticoagulants that inhibit clot formation through interactions with antithrombin and heparin cofactor II. Unfractionated heparin, low molecular weight heparin and heparin-derived drugs are often the main treatments used clinically to handle coagulatory disorders. A wide range of proteins have been reported to bind and neutralise these GAGs to promote clot formation. Such neutralising proteins are involved in a variety of other physiological processes, including inflammation, transport and signalling. It is clear that these interactions are important for the control of normal coagulation and influence the efficacy of heparin and heparin-based therapeutics. In additon to neutralisation, the anticoagulant activities of GAGs may also be regulated through reduced synthesis or by degradation. In this review we describe GAG neutralisation, the proteins involved and the molecular processes that contribute to the regulation of anticoagulant GAG activity.