Thrombin, a multifunctional protease generated at sites of vascular injury, is a powerful agonist for a variety of cellular processes important in cardiovascular disease. A recently cloned thrombin receptor has provided a framework for understanding how thrombin, a protease rather than a classic ligand, activates cells. It has also yielded new tools for defining the role of thrombin and its receptor in cellular events. This review discusses a working model for how thrombin activates platelets and other cells, and possible roles for the thrombin receptor in thrombotic, proliferative, and inflammatory processes.