Water immersion skin wrinkling is an indicator of limb sympathetic function. Routine clinical usage of this enigmatic phenomenon is hampered by poor endpoint quantification, which involves counting skin folds. The recent discovery of the importance of vasoconstriction in immersion wrinkling suggests digital blood flow or volume changes as better endpoints. Water probably initiates the wrinkling process by altering epidermal electrolyte homeostasis as it diffuses into the porous skin of the hands and soles via its many sweat ducts. Altered epidermal electrolyte homeostasis would lead to a change in membrane stability of the surrounding dense network of nerve fibers and trigger increased vasomotor firing with subsequent vasoconstriction. Vasoconstriction, through loss of volume, leads to negative digit pulp pressure resulting in a downward pull on the overlying skin, which wrinkles as it is distorted. The degree of wrinkling would directly depend on the change in digit tip volume and implies any process inducing loss of digit volume will precipitate wrinkling. This review discusses the physiology of water immersion wrinkling and explores its potential as an indicator of limb sympathetic dysfunction.