Comfort may be considered as the material aspect of well-being, and its limitation, defined as discomfort, exacerbates both the patient's and caregivers' difficulties. Discomfort results from the interaction of a patient's environment, treatment, and from the nature and severity of elementary deficits, such as spasticity, ranges of motion, pain, postural disorders, motor deficit and fatigue, bladder problems, insufficient ventilatory control, and also psychological difficulties. Although discomfort reduction may represent a major challenge in disabled persons, discomfort is usually underestimated in the assessment of deficiencies, disabilities, handicap, and even in quality of life (QOL) estimations. In this paper, we explain why discomfort may be a crucial problem in severe multiple sclerosis (MS) and argue for a systematic assessment of discomfort in the follow-up of the disease, especially in the following domains: dressing, washing, maintaining posture in a wheelchair and bed, food intake, mastication and swallowing, bowel control, urinary and feces emission, and also sexual life. The way to enhance comfort in MS patients is then analyzed.