Spiders have been incriminated as causes of human suffering for centuries, but few species worldwide cause medically significant envenomation. Widow spiders (Latrodectus spp.) occur worldwide and cause latrodectism, which is characterized by pain (local and generalized) associated with nonspecific systemic effects, diaphoresis, and less commonly other autonomic and neurological effects. Recluse spiders (Loxosceles spp.) are distributed mostly through the tropical and subtropical Western Hemisphere and can cause severe skin lesions and rarely systemic effects; most bites are unremarkable. Highly dangerous spiders in South America (armed spiders) and Australia (funnel-web spiders) cause rare but severe envenomation requiring medical intervention and sometimes antivenom. Most other spiders involved in verified bites cause minor, transient effects. Many spiders blamed for causing medical mischief have been elevated to medical significance via circumstantial evidence, poor reporting, and repetitive citation in the literature; several species have been shown to be harmless with more stringent scientific evidence involving verified bites in humans.