Multiple sclerosis (MS) is a demyelinating and debilitating disease characterised by a range of symptoms such as motor dysfunction and muscle weakness. A significant MS symptom is heat sensitivity so that exposure to heat will increase body temperature and consequently the appearance of neurological signs. Although some people with MS can undertake exercise, it is thought to be limited by the sensitivity to heat and the subsequent rise in body temperature which occurs. It has been found that central fatigue is a determining factor in muscle activation and performance in normal healthy subjects. However, it is unknown whether thermal strain also induces central fatigue in MS even though muscular fatigue in MS is due mainly to central rather than peripheral factors. This review focuses on the similarities in the manifestation of central fatigue in both MS and healthy subjects with reference to thermal strain and heat reactions.