Water, the main component of the body, is distributed in the extracellular and intracellular compartments. Water exchange between these compartments is mainly governed by osmotic pressure. Extracellular water osmolarity must remain within very narrow limits to be compatible with life. Older adults lose the thirst sensation and the ability to concentrate urine, and this favours increased extracellular osmolarity (hyperosmotic stress). This situation, in turn, leads to cell dehydration, which has severe consequences for the intracellular protein structure and function and, ultimately, results in cell damage. Moreover, the fact that water determines cell volume may act as a metabolic signal, with cell swelling acting as an anabolic signal and cell shrinkage acting as a catabolic signal. Ageing also leads to a progressive loss in muscle mass and strength. Muscle strength is the main determinant of functional capacity, and, in elderly people, depends more on muscle quality than on muscle quantity (or muscle mass). Intracellular water content in lean mass has been related to muscle strength, functional capacity, and frailty risk, and has been proposed as an indicator of muscle quality and cell hydration. This review aims to assess the role of hyperosmotic stress and cell dehydration on muscle function and frailty.