BACKGROUND Effective antiseptic to reduce surgical site infections is a cornerstone of modern surgery. Chlorhexidine gluconate–based antiseptics are among the most effective of these products. Unfortunately, chlorhexidine solutions are toxic to the cornea and middle ear, and they pose a splash risk to both the patient and health care personnel. OBJECTIVE To examine the clinical evidence that led to the disavowal of chlorhexidine antiseptic solution for use on the face and head. METHODS AND MATERIALS Reference searches were performed using PubMed, Embase, and LexisNexis databases without restriction to the date of publication, language, or study setting. RESULTS The literature revealed 11 sentinel cases of severe chlorhexidine-related keratitis in the late 1980s. These cases are reviewed together with data on ototoxicity and alternative products to understand why chlorhexidine solution should not be used on the face and scalp. CONCLUSION Chlorhexidine antiseptic solutions are highly effective. However, they pose a risk to the middle ear and have the potential to irreversibly damage the cornea with a minimal splash exposure. Povidone–iodine is a safe and effective alternative.