Intravascular administration of contrast media may inadvertently result in adverse drug reactions (ADR) including selected hypersensitivity reactions. This review highlights some very rare ADR, aiming to alert imaging physicians to these conditions and to prompt adequate management. This is particularly relevant for Kounis syndrome, an immediate hypersensitivity reaction involving the coronary arteries. The acute management of Kounis syndrome can be challenging, as it requires continued contrast media administration, while balancing the simultaneous coronary reperfusion that requires vasodilatation with anti-allergic treatment that may involve vasoconstrictor agents. For other adverse reactions, referral to a drug allergy specialist is highly recommended to assess causality and identify safe alternatives. Clinical Relevance Statement: Cardiologists and radiologists must recognize the key symptoms of these very rare adverse reactions to contrast media to promptly initiate the appropriate therapy and refer patients for allergological evaluation, ideally within 1–6 months after the reaction.</p