Diabetes mellitus is associated with a series of macrovascular and microvascular changes that can manifest as a wide range of complications. Foot ulcerations affect ∼2-4% of patients with diabetes mellitus. Risk factors for foot lesions include peripheral and autonomic neuropathy, vascular disease and previous foot ulceration, as well as other microvascular complications, such as retinopathy and end-stage renal disease. Ulceration is the result of a combination of components that together lead to tissue breakdown. The most frequently occurring causal pathways to the development of foot ulcers include peripheral neuropathy and vascular disease, foot deformity or trauma. Peripheral vascular disease is often not diagnosed in patients with diabetes mellitus until tissue loss is evident, usually in the form of a nonhealing ulcer. Identification of patients with diabetes mellitus who are at high risk of ulceration is important and can be achieved via annual foot screening with subsequent multidisciplinary foot-care interventions. Understanding the factors that place patients with diabetes mellitus at high risk of ulceration, together with an appreciation of the links between different aspects of the disease process, is essential to the prevention and management of diabetic foot complications.