Healing of diabetic foot ulcers is limited by multiple factors and therefore therapeutic strategies require a multifactorial approach. Reduction of the amputation rates is one of the primary goals. Up to 70% of all lower-leg amputations are performed on people with diabetes, and more >1 million people undergo a lower-limb amputation as a consequence of diabetic foot syndrome (DFS) every year. Lifelong observation and continuity of care of people with a foot at risk are essential in both prevention and management. The important principles are regular inspection, cleansing, removal of debris and/or regular debridement with a scalpel. The principles of care of diabetic foot ulcer are (1) treatment of any associated infection, (2) revascularization if feasible, (3) off-loading, and (4) management of the wound bed in order to promote healing. Adequate pressure relief is an essential component of successful and consistent healing for the majority of neuropathic diabetic foot ulcers. Every diabetic foot wound should be assessed routinely for the presence of infection. The diagnosis of infection in DFS is based on clinical findings of inflammation. Infected diabetic foot ulcers often require surgical therapy and hospital stay. In DFS, the rate of ulcer recurrence are 27% in the first year and 100% after 4 years.