Critical limb ischaemia (CLI) is a manifestation of peripheral arterial disease (PAD) that describes patients with chronic ischaemic rest pain, or patients with ischaemic skin lesions, either ulcers or gangrene. The clinical diagnosis of CLI should be confirmed by haemodynamic parameters such as the ankle- or toe systolic pressure. The estimated annual incidence of CLI ranges between 500 and 1 000 new cases per 1 million, with diabetes being the most important risk factor. CLI is also a marker for mostly generalized and severe atherosclerosis, and therefore the prognosis of patients is poor concerning overall survival. The primary goals of treatment in patients with CLI are to relieve ischaemic pain, heal ulcers, prevent limb loss, improve patient function and quality of life and prolong overall survival. Any kind of revascularization should be done whenever technically possible, and therefore most patients should be referred to a vascular center. Furthermore, in patients with CLI a multidisciplinary approach is recommended to control pain, cardiovascular risk factors and other co-morbid disease. In patients with CLI not eligible for arterial revascularization, prostanoids are the only vasoactive drugs with proven efficacy. The safety and efficacy of the various forms of therapeutic angiogenesis still have to be proven before one can conclude on its role as an additional limb saving strategy.