There has been a marked expansion of the indications for oral anticoagulant therapy, particularly among the elderly. Despite the documented benefits, the use of warfarin remains strikingly low among patients 80 years of age and older. Elderly patients often exhibit an enhanced dose response to warfarin. On average, steady-state warfarin doses decrease by 11% per decade of age. Pharmacokinetic changes in the elderly are negligible. Pharmacodynamic differences have not been well characterized. Initiating warfarin dosing in the elderly should be done cautiously, with doses of 5 mg or less. Doses should be adjusted downward in the presence of congestive heart failure, advanced obstructive lung disease, liver disease, malignancy, protracted diarrhea, enteral feedings, or concurrent potentiating medications. Numerous medications interfere with the anticoagulant response of warfarin. The most powerful potentiating drugs are those that interfere with the metabolism of (S)-warfarin. Examples include amiodarone, trimethoprim-sulfamethoxazole, and metronidazole. These drugs should be prescribed with caution in the elderly and mandate frequent INR monitoring during the induction period. An extensive assessment of patient-specific factors that might increase the hazards related to warfarin therapy needs to be conducted and documented before initiating oral anticoagulant therapy. Patients and their caregivers need to understand the risks and benefits, and to recognize signs of abnormal bleeding and the need for frequent monitoring. Patients should be encouraged to maintain consistency in their vitamin K intake and should strive to meet the recommended dietary allowance for vitamin K. To improve anticoagulation control, physicians and other health care providers need to be aware of the many warfarin drug interactions and be cognizant of the increased dose response of warfarin seen in the elderly. Concurrent prescription of multiple drugs known to affect warfarin's anticoagulant response should be minimized and use of nonselective nonsteroidal anti-inflammatory drugs should be limited given their deleterious effects on the gastric mucosa. Transitions from inpatient care to subacute care and back to outpatient care are particularly vulnerable periods for patients' anticoagulation control. Enhanced provider communication and more seamless transitions help to ensure optimal INR follow-up and timely warfarin dose adjustment if indicated.