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Spider venom is being researched for its potential use in applications such as insecticides, to better understand the dynamics of neuronal ion channel physiology and as potential remedies to counter antibiotic resistant bacteria. However, spider venom is more widely known for its ability to cause deleterious reactions after toxic envenomations in humans. In this short review, the “dark” side of spider venoms is presented to provide a counterbalance to the investigations of the positive potential that venoms can or might improve our world or its understanding. The goal was to present a short primer on species having clinical consequences in humans rather than be an exhaustive review of all spiders of medical importance.Envenomation signs and symptoms for several spider species are given.Signs and symptoms differ significantly among the spider taxa.Misdiagnosis of medical conditions as spider bites is a recurring problem leading to potential mistreatment of patients.