Organisms exposed to altered salinity must be able to perceive osmolality change because metabolism has evolved to function optimally at specific intracellular ionic strength and composition. Such osmosensing comprises a complex physiological process involving many elements at organismal and cellular levels of organization. Input from numerous osmosensors is integrated to encode magnitude, direction, and ionic basis of osmolality change. This combinatorial nature of osmosensing is discussed with emphasis on fishes.