AbstractWater channels or water channel proteins (WCPs) are transmembrane proteins that have a specific three‐dimensional structure with a pore that can be permeated by water molecules. WCPs are large families (over 450 members) that are present in all kingdoms of life. The first WCP was discovered in the human red blood cell (RBC) membrane in 1980s. In 1990s other WCPs were discovered in plants, microorganisms, various animals, and humans; and it became obvious that the WCPs belong to the superfamily of major intrinsic proteins (MIPs, over 800 members). WCPs include three subfamilies: (a) aquaporins (AQPs), which are water specific (or selective water channels); (b) aquaglyceroporins (and glycerol facilitators), which are permeable to water and/or other small molecules; and (c) “superaquaporins” or subcellular AQPs. WCPs (and MIPs) have several structural characteristics which were better understood after the atomic structure of some MIPs was deciphered. The structure–function relationships of MIPs expressed in microorganisms (bacteria, archaea, yeast, and protozoa), plants, and some multicellular animal species [nematodes, insects, fishes, amphibians, mammals (and humans)] are described. A synthetic overview on the WCPs from RBCs from various species is provided. The physiological roles of WCPs in kidney, gastrointestinal system, respiratory apparatus, central nervous system, eye, adipose tissue, skin are described, and some implications of WCPs in various diseases are briefly presented. References of detailed reviews on each topic are given. This is the first review providing in a condensed form an overview of the whole WCP field that became in the last 20 years a very hot area of research in biochemistry and molecular cell biology, with wide and increasing implications. © 2009 IUBMB IUBMB Life, 61(2): 112–133, 2009