Acute Charcot neuroarthropathy of the foot and ankle is often difficult to diagnose because of limited findings in the patient history, physical examination, imaging, and laboratory studies. Delay in treatment results in the development of rigid foot and ankle deformities, increasing the risk of ulceration, infection, and major lower extremity amputation. Acute Charcot neuroarthropathy should be suspected in any patient 40 years or older with obesity and peripheral neuropathy who presents with an acutely swollen foot following minimal or no recalled trauma and who reports minimal to no pain, particularly if radiography and laboratory markers of infection are normal. Magnetic resonance imaging or computed tomography should be performed in these cases. If changes consistent with acute Charcot neuroarthropathy are observed, prompt immobilization and/or referral to a foot and ankle subspecialist is needed to minimize sequelae. Immobilization should continue until lower extremity edema and warmth resolve, and serial radiography shows evidence of osseous consolidation. Intranasal calcitonin salmon may have a role as adjunctive therapy. Although controversial, surgery may be indicated if there is severe dislocation or instability, concern for skin breakdown, or failure of conservative treatment to obtain a stable, plantigrade foot.