Loxosceles spiders are of concern outside of the arachnological world because their bites can cause occasional necrotic skin lesions and/or systemic complications; these manifestations are known as loxoscelism. Once these spiders became well associated as medical entities, much notoriety was attained through the publication of medical case histories as well as tales of horrific wounds in the general literature. Although most Loxosceles spider bites are unremarkable, require only general supportive care, and often result in excellent outcome, they are an occasional source of severe dermonecrotic injury with long healing times and significant scarring. In rare cases of systemic loxoscelism, serious intravascular, nephrological and/or multi-organ damage can occur, sometimes resulting in death. However, also of concern is that loxoscelism is diagnosed by medical personnel or presumed by the general public in highly improbable scenarios preventing or delaying proper remedy, which can lead to deleterious outcome. Herein, Loxosceles spider biology and medical aspects are reviewed. In particular, an extensive discussion of the distribution of the brown recluse spider, L. reclusa Gertsch & Mulaik 1940, is presented along with life history characteristics, which relate to the medical aspects of the genus. Also presented are manifestations and epidemiology of loxoscelism, misdiagnoses of bites by the medical community, alternative diagnoses confused with recluse spider bites and a discussion of the psychological basis for the proliferation of the myth of loxoscelism by both the general public and the medical community. North and South American species are reviewed because this is where the genus predominates and is the region where the most pertinent research has originated.