Chronic limb ischemia or chronic peripheral artery disease (PAD) covers the obliterating diseases of the arteries of the limbs from asymptomatic to symptomatic, and in common practice we most often refer of atherosclerotic disease. Symptomatic affection is manifested by claudication, the most severe clinical form of which is resting limb pain or the presence of defects – known as critical limb ischaemia. Critical limb ischaemia (CLI) or chronic limb threatening ischaemia (CLTI) is considered the most severe pattern of peripheral artery disease (PAD). It is defined by the presence of chronic ischemic rest pain, ulceration or gangrene (chronic limb threatening ischemia) attributable to the occlusion of peripheral arterial vessels. It is associated with a high risk of major amputation, cardiovascular events, and death. However, despite the technological advances to manage CLI with minimally invasive technologies, this condition often remains untreated. In this review, we presented a complete overview of the physiopathology, diagnosis and holistic management of CLI. Revascularization is the first-line treatment, but several challenging cases are not treatable by conventional techniques. In diabetic patients, it is important to keep in mind some specificity of clinical findings and therapy. An interdisciplinary approach is mandatory.