Aquaporins (AQP) are a family of hydrophobic intrinsic membrane proteins that efficiently and selectively transport water. Since the discovery of first water channel (AQP1) from red blood cell membrane by Agre et al in 1992, rapid and serial progresses have been made in characterization of AQP structure and function. At least 11 homologous members (AQP0 - AQP10) have been molecularly identified in mammals. AQPs are expressed in various epithelium and endothelium involving fluid secretion and absorption, and in many cell types such as erythrocytes, white blood cells, adipocytes, and muscle fibers that have no obvious relationship with fluid transport. The extensive expression pattern of AQPs may indicate functional importance in multiorgan physiology and pathophysiology. Gene-targeting technology has been a powerful tool in defining physiological functions of specific genes. So far transgenic knockout models of AQP1, AQP3, AQP4 and AQP5, and a knock-in model introducing a point mutation (T126M) that causes autosomal recessive nephrogenic diabetes insipidus (NDI) in human have been successfully established. Significant progresses have been made in characterizing the physiological functions of these AQPs by systematic mouse phenotype studies.