Peripheral arterial disease (PAD) is a common circulatory disorder of the lower limb arteries that reduces functional capacity and quality of life of patients. Despite relatively effective available treatments, PAD is a serious public health issue associated with a significant morbidity and mortality. Ischemia-reperfusion cycles occurring during PAD are responsible for insufficient oxygen supply, mitochondriopathy, free radical production, inflammation and lead events that contribute to myocyte death and remote organ failures. However, the mitochondrial and cellular chronological events that occur during the ischemic period and at the moment of reperfusion have been poorly reviewed in skeletal muscle fibers. Thus, after a review of the basal myocyte state and the normal mitochondrial biology, we will discuss the physiopathology of ischemia and reperfusion from a mitochondrial and cellular point of view. We will first describe the chronology of the deleterious biochemical and mitochondrial mechanisms activated by ischemia-reperfusion. We will then develop skeletal muscle ischemia-reperfusion injury to the muscle environment, mitochondrial dynamics and inflammation. A better chronological understanding of the events underlying ischemia-reperfusion will allow us to identify key actors in the development of this pathology and point to new suitable therapies. Emerging data on mitochondrial dynamics should identify new molecular and therapeutic targets and develop protective strategies against PAD.