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Toxic keratoconjunctivitis (TK) is an underrecognized complication of ophthalmic drug use and various environmental or occupational exposures. A detailed history and clinical examination are important to identify the offending agent(s). Common drug-related causes of TK include preservatives in ophthalmic medications, topical antimicrobials, and topical anesthetics. Alternatives to benzalkonium chloride as well as preservative-free formulations should be considered in patients requiring long-term topical medication. More advanced cases of TK may require preservative-free topical steroids and/or antibiotics, and occasionally surgical intervention. Early recognition and appropriate management of TK may help prevent permanent ocular and visual damage.