Diabetic foot ulcers (DFUs) are a common and serious complication of diabetes mellitus. A review of the literature confirms that the presence of an unhealed DFU negatively affects several domains of patient quality of life (daily and social activities) and increases the risk of infection, amputation, and death. Patients with diabetes mellitus and DFUs also have higher healthcare utilization rates than patients without DFUs and reported healing rates vary from 24% to 82% after 12 weeks of care. Guidelines for the expeditious healing of DFUs are available and include debridement, infection control, offloading, and the use of dressings that maintain a moist wound bed. Wound measurements to determine progress toward healing must be obtained because percent reduction in wound area during the first 4 weeks of care is a predictor of treatment outcome. If a wound fails to respond to standard care, the use of advanced treatment approaches such as cytokines, negative pressure therapy, and living skin equivalents may be beneficial. Clinical studies to further elucidate the effects of topical, systemic, and supportive regimens of care on outcomes and costs are needed.