Most dairy cows experience some degree of hypocalcemia during the periparturient period. There is, however, a sub-group of dairy cows that experience a breakdown in their ability to maintain plasma calcium and, consequently, suffer from severe hypocalcemia. This condition is also known as milk fever and usually occurs in cows in their third or greater lactation. The precise metabolic lesions responsible for the onset of milk fever have not yet been defined. Research has shown that milk fever is not the result of inadequate production of calcitropic hormones (parathyroid hormone and 1,25-dihydroxyvitamin D), but rather is more likely a result of inadequate receptor numbers or receptor dysfunction in the target cell of these hormones. This report reviews vitamin D and calcium metabolism, giving emphasis to 1,25-dihydroxyvitamin D receptor regulation and function as related to the periparturient dairy cow. The report also focuses on providing insights into nutritional (anionic diets) and endocrine strategies that have proved useful in milk fever management.