Aquaporins (AQPs) are a large family of membrane proteins that act as semipermeable channels. The majority of AQPs are permeable to water, but a subset of the family can also transport glycerol, urea, and other small solutes. Currently, 13 AQP homologues have been identified in mammals, termed AQP0–12. These aquaporins are highly abundant in epithelial cells and non-epithelial cells in various tissues including the kidney, brain, liver, lungs, and salivary glands. In this chapter we focus on AQPs expressed in kidney epithelial cells. We summarize the current knowledge with respect to their localization and function within the kidney tubule and their critical role in mammalian water homeostasis. We describe a number of water balance disorders resulting from altered AQP function and provide an overview of some of the treatment strategies for these disorders.