The elderly are particularly sensitive to delirium-inducing medications. We report a case of a 93-year-old woman who developed anticholinergic delirium from subcutaneous diphenhydramine that she received in the emergency department. This patient was reportedly allergic to “caine” anesthetic agents, and thus, subcutaneous diphenhydramine was administered as an alternative local anesthetic, as recommended in emergency medicine textbooks. Within 20 minutes of administration, the patient developed agitation, tachycardia, dilated pupils, and dry skin, consistent with a classic anticholinergic toxidrome. Diphenhydramine use is associated with a high incidence of anticholinergic adverse effects, especially in the elderly. Clinicians should carefully consider using diphenhydramine in this vulnerable population.