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Background: Emerging evidence supports the view that (AQP) aquaporin water channels are regulators of transcellular\ud water flow. Consistentwith their expression in most tissues, AQPs are associatedwith diverse physiological\ud and pathophysiological processes.\ud Scope of review: AQP knockout studies suggest that the regulatory role of AQPs, rather than their action as passive\ud channels, is their critical function. Transport through all AQPs occurs by a common passive mechanism, but their\ud regulation and cellular distribution varies significantly depending on cell and tissue type; the role of AQPs in cell\ud volumeregulation (CVR) is particularly notable. This reviewexamines the regulatory role of AQPs in transcellular\ud water flow, especially in CVR.We focus on key systems of the human body, encompassing processes as diverse as\ud urine concentration in the kidney to clearance of brain oedema.\ud Major conclusions: AQPs are crucial for the regulation of water homeostasis, providing selective pores for the\ud rapidmovement ofwater across diverse cellmembranes and playing regulatory roles in CVR. Gatingmechanisms\ud have been proposed for human AQPs, but have only been reported for plant andmicrobial AQPs. Consequently, it\ud is likely that the distribution and abundance of AQPs in a particular membrane is the determinant of membrane\ud water permeability and a regulator of transcellular water flow.\ud General significance: Elucidating the mechanisms that regulate transcellular water flow will improve our understanding\ud of the human body in health and disease. The central role of specific AQPs in regulating water homeostasis\ud will provide routes to a range of novel therapies. This article is part of a Special Issue entitled Aquaporins.