The key reason behind the success of heparin in thrombosis and beyond is its polypharmacological sites of action for the prevention and treatment of multifactorial diseases that will only benefit slightly with single pharmacological mechanism-based agents. Thromboembolic disorders are driven by hypercoagulable, hyperactive platelet, proinflammatory, endothelial dysfunction, and proangiogenesis states. Heparin can effectively modulate all of those multifactorial components, as well as the interface among those components.