For more than 50 years, vitamin K antagonists (VKAs) were the only available oral anticoagulants. Although several drugs in this class were developed and used clinically (e.g., acenocoumarol, phenprocoumon), warfarin is the best known and most widely used. Warfarin is popularly known by its brand name Coumadin (branded by Endo in the 1950s, acquired by DuPont in 1969 and Bristol Myers Squibb in 2001) [1]. Since it came into use, much has been learned about its mechanism of action, pharmacology, and pharmacodynamics. VKAs are multitargeted and lower the activity of four vitamin K–dependent coagulation factors that promote blood clotting, factors II, VI, IX, and X, and two anticoagulant proteins, protein C and protein S. Remarkably, it took until 2004 for the liver enzyme that is inhibited by VKAs, vitamin K epoxide reductase (VKORC1), to be molecularly identified [2]. As the VKAs have a narrow therapeutic window and individuals vary widely in responsiveness, its effect must be monitored using the prothrombin time (PT) test. It took years of clinical and laboratory investigation to standardize and optimize the monitoring of VKAs to achieve the best possible outcomes with respect to thrombosis prevention and a low bleeding rate. This was achieved by development of the international normalized ratio (INR), which is derived from the PT. Anticoagulation or Coumadin clinics that employ nurses and pharmacists skilled in managing warfarin have greatly improved the care of patients on warfarin. VKAs, however, can still be difficult to use safely, particularly in elderly patients with comorbidities and diminished cognition.