Early and accurate diagnosis of infection or neuropathy of the diabetic foot is the key to successful management. Angiopathy leads to ischemia which, in combination with peripheral neuropathy, predisposes to pedal skin ulceration, the precursor of osteomyelitis. Chronic hyperglycemia promotes production of glycosylated end products which accumulate on endothelial proteins, causing ischemia of the vasa nervorum. When combined with axonal degeneration of the sensory nerves, the result is hypertrophic neuroarthropathy. Should the sympathetic nerve fibers also be damaged, the resultant loss of vasoconstrictive impulses leads to hyperemia and atrophic neuroarthropathy. Plain radiography, although less sensitive than radionuclide, magnetic resonance (MR), and computed tomographic examinations, should be the initial procedure for imaging suspected osteomyelitis in the diabetic patient. If the radiographs are normal but the clinical suspicion of osteomyelitis is strong, a three-phase 99mTc-MDP scan or MR imaging is recommended. An equivocal 99mTc-MDP scan should be followed by MR imaging. To exclude osteomyelitis at a site of neuroarthropathy, a 111In white blood cell scan is preferable. To obtain a specimen of bone for bacteriological studies, percutaneous core biopsy is the procedure of choice, with the entrance of the needle well beyond the edge of the subjacent ulcer.