Heparin is a glycosaminoglycan well known for its anticoagulant properties. In addition, heparin possesses anti-inflammatory effects. Although the mechanisms responsible for the anticoagulant effects of heparin are well understood, those underlying its anti-inflammatory effects are not. This review presents some of the evidence from clinical and animal studies supporting an anti-inflammatory role for heparin and heparin-related derivatives. Potential mechanisms by which heparin can exert its anti-inflammatory effects are discussed. The clinical use of heparin as an anti-inflammatory agent has been held back by the fear of bleeding. Development of nonanticoagulant heparins or heparin derivatives should mitigate this concern.