The high water permeability of certain biological membranes is due to the presence of aquaporin water channel proteins. Thirteen homologs have been identified in humans. These are selectively permeated by water (aquaporins) or water plus glycerol (aquaglyceroporins). The sites of expression predict the clinical phenotypes in humans. Individuals lacking Colton blood group antigens have mutations in the AQP1 gene. When deprived of water, they exhibit a defect in urine concentration and a marked reduction in fluid exchange between capillary and interstitium in lung. AQP0 is expressed in lens fiber cells and mutations result in familial cataracts. AQP2 is expressed in renal collecting duct principal cells where membrane trafficking is regulated by vasopressin. Mutations in the human AQP2 gene result in nephrogenic diabetes insipidus, but underexpression is found in clinical disorders with reduced urinary concentration (lithium therapy)and overexpression is found in disorders with fluid retention (congestive heart failure). AQP5 is expressed in the apical membranes of salivary and lacrimal gland acini, and mistargetting has been identified in some patients with Sjogren's syndrome. Involvement of aquaporins 4, 5, 6, 7 and 9 is expected in several other human clinical disorders. Permeation by gases is an interesting development in mammalian aquaporin biology led by Gros, Boron, and colleagues. Other physiological roles of aquaporins are being pursued by multiple laboratories worldwide.