Necrotic arachnidism is the potential cutaneous reaction to spider bite venom. In the United States, members of 7 spider families may be responsible for envenomation sufficiently severe to warrant treatment. Characteristics of several spiders, in particular Loxosceles spiders, whose bite is toxic to humans are described, and diagnostic standards, preventive measures, and treatment options are reviewed. (J Am Acad Dermatol 2001;44:561-73.) Learning objective: After the completion of this learning activity, participants should be familiar with the characteristics of several different spider families endemic to the United States. Furthermore, this learning activity should aid in the prevention and diagnosis of spider bites as well as in the classification and treatment of specific bites.