Among its many functions, the kidney regulates water and sodium excretion, both of which have significant consequences for whole-body homeostasis. A failure to conserve water can lead to death due to dehydration, and a failure to excrete sufficient quantities of sodium can lead to hypertension. To date, mathematical models of renal function have typically treated the kidney as either a "black box", or as a single (homogeneous) nephron. In either case, such models are ill-equipped to predict the consequences of functional changes in the kidney, which may arise in response to neurohumoral regulation, genetic disorders, gene knockouts, the onset of a renal or extra-renal pathology, or the administration of pharmacological interventions. I will discuss our efforts to build a whole-kidney model that explicitly represents the tubular and vascular architecture of the kidney, and which can accurately predict renal water and sodium excretion over a range of physiological conditions.