Traditionally, arginine vasopressin modulation of renal water, sodium, and urea excretion has been considered somewhat in isolation from factors that control divalent mineral ion homeostasis. Similarly, previous considerations of divalent mineral ion metabolism have focused mainly on the role of hormones, eg, parathyroid hormone and various forms of vitamin D, as principal modifiers of renal calcium handling. Recent data, however, have now suggested the existence of novel linkages that coordinate control of water and divalent mineral ion homeostasis. This article summarizes these data and highlights the fundamental roles of the extracellular calcium polyvalent cation-sensing receptor (CaR) as an integrator of water and divalent mineral ion homeostasis on a cellular, organ-specific, and whole-body basis. Organs where CaRs may integrate water and divalent mineral ion metabolism include endocrine tissues that express CaRs, the brain, various nephron segments of the kidney, bone, and the gastrointestinal tract. These new data suggest that considerable regulatory overlap exists between water and divalent mineral ion homeostasis.