Vancomycin is a powerful glycopeptide antibiotic that is increasingly being used owing to the emergence of highly resistant organisms such as methicillin-resistant Staphylococcus aureus. Although a generally safe medication, administration of vancomycin is not benign, and there have been a number of adverse reactions reported. We present the case of a patient with vancomycin-induced red man syndrome who developed vancomycin anaphylaxis. Our case illustrates that red man syndrome may be a marker for true vancomycin allergy, although it was generally not thought of as so in the past.