Movement of urea across plasma membranes is modulated by specialized urea transporter proteins. Two urea-transporter genes have been cloned: UT-A (Slc14a2) and UT-B (Slc14a1). In the mammalian kidney, urea transporters are essential for the urinary concentrating mechanism and maintaining body fluid homeostasis. In this article, we discuss (1) an overview of historic discoveries in urea transport mechanisms; (2) an overview of recent discoveries in the regulation of urea transporters; (3) physiological studies in UT-A1/3 (-/-) mice highlighting the essential role of urea transporters in the urinary concentrating mechanism; and (4) physiological studies in UT-A2 and UT-B knockout mice examining the role of countercurrent exchange in the production of a maximally concentrated urine.