Neuropathy and ischemia, two common complications of diabetes mellitus, are the primary underlying risk factors for the development of foot ulcers and their complications. The presence of symmetric distal polyneuropathy, encompassing motor, sensory, and autonomic involvement, is one of the most important factors in the development of diabetic foot ulcers. Perhaps one third of diabetic foot ulcers have a mixed neuropathic and ischemic etiology. Although neuropathy and ischemia are the primary predisposing factors in the formation of diabetic foot ulcers, an initiating factor, such as physical or mechanical stress, is required for an ulcer to develop. Ischemic ulcers develop as a result of low perfusion pressure in a foot with inadequate blood supply, whereas neuropathic ulcers result from higher pressures in a foot with adequate blood supply but loss of protective sensation. In addition to increasing the risk of ulceration, diabetes mellitus also increases the risk of infection by impairing the body's ability to eliminate bacteria. The processes by which ulcers develop are reviewed here.