Management of diabetic foot ulcers remains a rather challenging task. Epidermal growth factor (EGF) plays a central role in wound healing. It acts on epithelial cells and fibroblasts promoting restoration of damaged epithelium. However, its bioavailability is impaired in chronic diabetic foot ulcers. Current evidence suggests that application of human recombinant EGF in addition to standard treatment is able to achieve both partial and complete healing and to prevent foot amputations. Its efficacy has been tested at various concentrations and by various administration routes (topical application and intralesional injection). Intralesional injection has better availability on the deep wound layers, but pain at the injection site is a common complaint. Generally, adverse events have been minor to mild. Finally, numerous issues need to be further clarified before widespread use of EGF becomes possible in everyday practice. Such issues include optimal dosage and administration route, characteristics of the ulcers most likely to heal (severity and ischemic/neuropathic or both), and cost-effectiveness.