Urea transporters (UTs) are a group of membrane channel proteins that specifically facilitate the permeation of urea, which play an essential role in urea reabsorption and water conservation. There are 4 isoforms, UT-A1, UT-A2, UT-A3, UT-B, that are expressed in the kidney to maintain the urea recycle and establish the urea concentration gradient in the medulla, which is essential for the urinary concentration capacity of the kidney. Outside the kidney, widely distributed UT-B and some UT-A isoforms directly participate in regulating signaling transduction and determining cell fate by regulating osmotic pressure, arginine metabolism, and protein carbamylation in various systems. In recent years, studies on different UT knockout mouse models revealed multiple physiological roles of UTs. This chapter summarizes the physiological functions of UTs, including the blood system, urinary system, nervous system, circulatory system, digestive system, auditory system, visual system, reproductive system, and skeletal system.