Narrow therapeutic index (NTI) drugs are agents for which small changes in systemic concentration can lead to significant changes in pharmacodynamic response. This may result in potentially subtherapeutic or toxic effects, particularly in patients with advanced age, comorbid illness, or those receiving multiple medications. Bioequivalence among generic and innovator drug products does not always ensure therapeutic equivalence, especially with regard to NTI drugs. Warfarin is a NTI drug for which substitution is now available and may occur routinely without the knowledge of the patient or practitioner. To avoid overanticoagulation or underanticoagulation, the additional cost of patient education and monitoring may actually exceed cost savings by using the less expensive generic drug product. When brand name drug is preferred by the practitioner, “no substition” must be specified on the prescription to avoid mandated generic interchange of warfarin and other NTI drugs.