Generic substitution of narrow therapeutic index drugs can have unintended consequences. Generic switching is often driven by cost incentives, regulations and supply, but may raise concerns about equal bioavailability, therapeutic equivalence and about possible confusion for the patient. Integrated systems of care with active management of patient behaviors, including adherence, may minimize the impact of switching. This article is intended to present policy drivers and potential consequences of generic switching and the role of pharmacist education in minimizing patient risk using warfarin and the pharmaceutical distribution systems of the United States and Germany as examples.