We recommend changing the name of the milk-alkali syndrome to the calcium-alkali syndrome, because the new terminology better reflects the shifting epidemiology and understanding of this disorder. The calcium-alkali syndrome is now the third most common cause of hospital admission for hypercalcemia, and those at greatest risk are postmenopausal or pregnant women. The incidence of the calcium-alkali syndrome is growing in large part as a result of the widespread use of over-the-counter calcium and vitamin D supplements. Advertising for treatment or prevention of osteoporosis has long encouraged this use. Intricate mechanisms mediating the calcium-alkali syndrome depend on interplay among intestine, kidney, and bone. New insights regarding its pathogenesis focus on the key role of calcium-sensing receptors and TRPV5 channels in the modulation of renal calcium excretion. Restoring extracellular blood volume, increasing GFR and calcium excretion, and discontinuing calcium supplementation provide best treatment.