Because thrombin is central to the development and propagation of both arterial and venous thrombi, it is a logical therapeutic target. Direct thrombin inhibitors, such as ximelagatran, offer the distinct advantage of inhibiting fibrin-bound as well as free thrombin. The pharmacokinetics and pharmacodynamics of ximelagatran are predictable across a broad spectrum of patients. The half-life of melagatran, ximelagatran's active metabolite, is consistent with twice-daily dosing and fixed-dose administration without the need for monitoring. There have been no known drug interactions with ximelagatran, and the agent is not metabolized by the hepatic cytochrome P-450 system. For these reasons, orally active direct thrombin inhibitors such as ximelagatran will likely become the standard for long-term anticoagulation.