Osteomyelitis (bone infection) and neuro-osteoarthropathy (Charcot arthropathy) are limb-threatening complications of diabetic neuropathy with very different therapies. Distinguishing between them may be difficult, but it is important. In Charcot arthropathy, noninfectious soft tissue inflammation accompanies rapidly progressive destruction, first of joints, then of bone. This occurs in a well-vascularized and severely neuropathic, but nonulcerated, foot. In osteomyelitis, chronic soft tissue ulceration precedes infection of bone, which may be physically exposed. Magnetic resonance imaging and bone biopsy are the preferred diagnostic tests, provided adequate technical and interpretive skills are available.