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Flexor tendon sheath infections of the hand must be diagnosed and treated expeditiously to avoid poor clinical outcomes. Knowledge of the sheath's anatomy is essential for diagnosis and to help to guide treatment. The Kanavel cardinal signs are useful for differentiating conditions with similar presentations. Management of all but the earliest cases of pyogenic flexor tenosynovitis consists of intravenous antibiotics and surgical drainage of the sheath with open or closed irrigation. Closed irrigation may be continued postoperatively. Experimental data from an animal study have shown that local administration of antibiotics and/or corticosteroids can help lessen morbidity from the infection; however, additional research is required. Despite aggressive and prompt antibiotic therapy and surgical intervention, even otherwise healthy patients can expect some residual digital stiffness following flexor tendon sheath infection. Patients with medical comorbidities or those who present late with advanced infection can expect poorer outcomes, including severe digital stiffness or amputation.