The purpose of this presentation is to provide a comprehensive overview of diabetic foot ulcer disease. Foot ulceration in diabetics is the leading cause of lower extremity amputation in this population. The etiology of ulceration is multi-factorial. Peripheral neuropathy is the single most important causative factor. The lack of sensation essentially leads to pressure ulceration over bony prominences of the foot. Autonomic neuropathy contributes via skin dessication and fissure formation, which leads to bacterial invasion and infection. Lastly, infrapopliteal arterial occlusive disease is prevalent in diabetics, such that arterial insufficiency may be a contributory factor. Treatment of diabetic ulceration is complex. It is essential to fully assess the wound and rule out complicating factors such as arterial insufficiency, osteomyelitis and plantar space abscess. If soft tissue infection exists, systemic antibiotic therapy is required. Exemplary wound care is necessary, including removal of all dead tissue, and provision of a moist wound environment supportive of heating. Most importantly, removing pressure from the foot (off-loading) is mandatory. Measures such as special shoes, crutches, walkers and wheelchairs may be necessary. Despite these efforts, many ulcers fail to heal. Research has demonstrated the importance of growth factors, such as platelet derived growth factor (PDGF) in wound healing regulation. Many chronic wounds have diminished growth activity compared to acute, healing wounds. These findings have provided the rationale for growth factor therapy for nonhealing diabetic ulcers. Recombinant human PDGF has been extensively evaluated in the United States via prospective, randomized, placebo- controlled, blinded studies. These studies have demonstrated that the use of PDGF, combined with good wound care, provides significant improvement in the rate of healing, as well as overall healing. Several clinical examples will be shown. Diabetic foot ulceration remains a difficult problem to manage. However, with newer biologic therapies, such as PDGF, better wound care can be provided by providing a more specific, physiologically directed treatment for these ulcers. As such, many patients will be spared operations to close these wounds, and potentially far fewer amputations will be required.