Since warfarin remains the predominate drug administered for long-term anticoagulation, optimizing therapy for maximum antithrombotic effect with minimal bleeding risk continues to challenge clinicians. Genetic differences exist that affect an individual's response to warfarin. The clinician can use genetic information in the future, along with current approaches to improved monitoring and dose schedules, to maintain even more successfully the appropriate therapeutic range for anticoagulation. The international normalized ratio (INR) is a good indicator of warfarin effect and addressing a high INR result often prevents bleeding complications. However, even with a therapeutic INR, patients are still at risk for bleeding. This review will discuss optimizing warfarin dosing, reducing an elevated INR, and managing the anticoagulated patient who has a bleeding event.