Acute, potentially life-threatening systemic reactions to contrast media are less frequent with lower osmolality, nonionic contrast agents, but they are not totally eliminated. Severe reactions remain a reality in all radiology departments. Typical reactions to contrast media include nausea and/or vomiting, scattered to extensive urticaria, bronchospastic reaction, hypotension (isolated) with compensating tachycardia, anaphylactoid reaction, vagal reaction, cardiovascular collapse, convulsion, and seizure. For each type of reaction, rapid recognition and initiation of specific corrective therapy enhance response and minimize side effects of drugs. Specific drugs for treating each reaction type are reviewed, including recommended dose, contraindications, and alternative choices. An approach to the high-risk patient and prevention of acute systemic reactions is discussed and pretreatment protocols are outlined.