Spiders of the genus Phoneutria, commonly known as wandering or banana spiders, are found in southern Central America (Costa Rica) and throughout South America east of the Andes into northern Argentina. Eight species, classified as Amazonian (P. fera, P. reidyi, and P. boliviensis) and non-Amazonian (P. keyserlingi, P. pertyi, P. eickstedtae, P. bahiensis, and P. nigriventer), have been described. Most of the clinically important bites by this genus occur in Brazil (~4,000 cases per year), with only 0.5% being severe. Local pain is the major symptom reported after most bites and involves peripheral (tachykinin (neurokinin NK 1 and NK 2) and glutamate receptors) and central (spinal) mechanisms (neurokinins, excitatory amino acids, nitric oxide, proinflammatory cytokines, and prostanoids). Other local features observed in envenomed patients include edema, erythema, radiating pain, sweating, fasciculation, and paresthesia. Systemic manifestations are less common and may include diaphoresis, tachycardia, arterial hypertension, agitation, prostration, sialorrhea, vomiting, tachypnea, pallor, hypothermia, cyanosis, diarrhea, and priapism. Shock and pulmonary edema, the main severe complications, are uncommon and possibly related to increased sympathetic activity and a systemic inflammatory response, although no sequential serum catecholamine, nitric oxide, and interleukin levels have been measured in prospective case series of human envenomations by Phoneutria spp. Most cases are treated symptomatically, with antivenom being recommended only for patients who develop important systemic clinical manifestations; such manifestations occur in~3% of cases and involve mainly children <10 years old and adults >70 years old. Fifteen deaths attributed to Phoneutria spp. have been reported in Brazil since 1903, but in only two of these cases are there sufficient details to confirm a causal nexus.