Anaphylaxis is a life-threatening, immunologically mediated reaction. "Anaphylactoid" reactions produce the same clinical syndrome but are not immunologically mediated. Vasoactive mediators of these reactions include histamine, eosinophilic chemotactic factors of anaphylaxis, slow reacting substance of anaphylaxis (a mixture of three leukotrienes, one a potent coronary vasoconstrictor), kinins, and prostaglandins. Symptoms usually occur within 15 minutes of parenteral injection of the causative agent, but can be delayed as long as 2.5 hours. Because vasodilation occurs at the capillary and postcapillary venule, resulting in loss of fluid and colloid (and hence reduction in effective plasma volume), and then shock, volume replacement is a mainstay of therapy. This article reviews the pathophysiology, incidence, and drug causes of anaphylactic/anaphylactoid reactions and proposes therapy to minimize the consequences of reactions seen by physicians treating spinal conditions.