Abstract :A variety of central nervous system (CNS) and non-CNS conditions leads to mobility impairment. In most cases, recovery and health benefits will critically depend upon regaining at least some mobility. However, after chronic immobilization or significantly impaired mobility problems, metabolic, cardiovascular, and muscular challenges are generally found. Among all therapeutic approaches that could be proposed, seeking a restored way of stepping on both feet is undoubtedly the first objective to be looking for. Foot skin health and integrity play a pivotal role in locomotion – it is the largest organ of the body and its constitutive structures and mechanisms are controlled by CNS and non-CNS systems. Some of these mechanisms become dysregulated after chronic immobilization, paralysis or mobility problems. Here, I summarize the main pathological conditions and cellular mechanism that could lead to dry foot skin problems and related-locomotor and rehabilitation concerns.