This review discusses the distinct envenomation syndromes produced by North American species of snakes and arthropods, specifically the Crotalinae subfamily of snakes, which includes cottonmouths, copperheads, and rattlesnakes; coral snakes; Latrodectus and Loxosceles species of arachnid; and Centruroides sculpturatus, the only species of North American scorpion capable of producing an envenomation syndrome. The authors discuss the epidemiology, pathophysiology, and presentation of these syndromes and emphasize the varying degrees to which these syndromes can manifest clinically. Finally, the management of each envenomation syndrome is addressed. Special attention is paid to available antivenoms, their indications for use, and their side effects.