Members of the spider genus Loxosceles (Araneae: Sicariidae) are found throughout the world. Their venom can cause severe open necrotic lesions in humans that can take several months to heal. Bite victims may also develop systemic reactions that can be life-threatening if medical attention is delayed or unavailable. Many Loxosceles species establish large populations in human habitats, creating a threat to human health and safety. Loxosceles reclusa, the brown recluse spider, is by far the most abundant spider species in many homes throughout the south-central United States. There has been an increase in awareness of brown recluse spiders, primarily due to negative media coverage of disfiguring bites and immense, slow-healing wounds. Although the bite of L. reclusa has been identified as a cause of necrotic lesions for nearly five decades, surprisingly few studies examine the biology of these spiders, and none have examined their association with humans. Few data have been published on the killing efficacy of pesticides on L. reclusa. Although millions of dollars are spent each year to control populations of L. reclusa in homes, no studies have been conducted to test newly developed chemicals or examine the benefits of integrated pest management practices. Here, we review historical accounts of pest management for L. reclusa populations and previous laboratory studies of biology and behavior. We then discuss how current studies of urban ecology, biological control, and urban pest management contribute to the management of L. reclusa populations in human habitats.