Generic drugs represent a significant portion of the medical arsenal in treating disease. As copies of originator drugs, these drugs have been permitted abbreviated approval under the Hatch-Waxman law. Yet with current drive toward lowering costs focusing upon generic formulation of drugs, potential safety issues have arisen. Although there is an established criterion of “bioequivalence” that generic formulations must demonstrate, narrow-therapeutic index drugs for sensitive disease states such as epilepsy, bleeding control, and mental health treatments may not be appropriate for application of generic bioequivalence levels of other generic drugs. Further, there is no mandate for comparison between different generic formulations. Indeed, countries outside the United States advocate for narrowing ranges of tolerability for these highly sensitive disease states and the drugs used to treat them. We argue in this paper that additional considerations as a patient safety matter must be taken into account for narrow therapeutic disease drugs, and that regulatory bodies should emphasize greater tightness in bioequivalence before these generic formulations are approved.