Ximelagatran, a direct thrombin inhibitor, is currently being considered by the US Food and Drug Administration (FDA) for approval as an anticoagulant to manage thromboembolic disorders and prevent systemic embolism in patients with atrial fibrillation. If ximelagatran is approved, clinicians will have to decide which patients are candidates for this therapy, how to switch patients from warfarin to ximelagatran, and, if necessary, how to switch patients from ximelagatran to warfarin. In addition, clinicians will need to consider their approach to treating patients with new-onset atrial fibrillation as well as conditions that may require an adjustment in dosing. This article highlights some of these issues as well as current data that provide guidance on how to manage them; however, answers to other questions will not be available until after the FDA approves the package insert material and data from the SPORTIF trial become available. Therefore, clinicians should diligently follow the medical literature regarding the latest information on this agent.