Formerly recognized primarily for its historic interest as a disorder found in those taking milk and bicarbonate for peptide ulcer disease, milk-alkali syndrome (MAS) is experiencing a resurgence in its incidence largely due to the increased usage of calcium carbonate. The modern version of MAS affects a different patient population and has a different etiologic basis than was characterized in the original descriptions of the syndrome. Advances in parathyroid hormone measurement have allowed for improved diagnostic separation between MAS and hyperparathyroidism and have further explained some of the physiologic responses in the resolution of hypercalcemia. We have reviewed the reasons for the increasing incidence of MAS, described the typical patient with the modern form of the syndrome, and further elaborated on the pathophysiology of MAS, as it is currently understood. MAS is an important diagnostic consideration in the patient with hypercalcemia because the syndrome is now common and prompt diagnosis limits permanent kidney function impairment but depends strongly on considering the diagnosis as well as obtaining an over-the-counter medication history.