A review of the literature confirms that the brown recluse spider bite is a common and sometimes serious clinical entity. Local and systemic manifestations are extremely variable, thus complicating management of the bite. Pathophysiological studies in laboratory animals yield conflicting results and therapeutic recommendations because of technical and species-specific differences. Standard therapies include aggressive, early debridement as well as systemic and intralesional corticosteroids; however, well-controlled clinical studies to establish their efficacy have not been performed. Variable and unpredictable patient responses to the spider bite necessitate a conservative yet vigilant position in managing these bites.