Adequate blood calcium concentrations are vital for the normal function of mammals. Mechanisms for maintaining normal blood calcium function adequately most of the time; however, occasionally they fail and calcium homeostasis is compromised. Milk fever or periparturient hypocalcemia in dairy cattle is a well-documented example of a breakdown in the mechanisms of calcium homeostasis. This disease occurs at the time of parturition and is unique to adult dairy animals. The disease results from the inability of animals to cope with the sudden demand for calcium in support of colostrum formation. Animals developing the disease become hypocalcemic and require intravenous calcium to survive. The precise metabolic disorder(s) responsible for the onset of milk fever is still being debated. This report will highlight some of the current concepts related to the causes and prevention of milk fever in dairy cattle, as well as contrasting differences in calcium demands that exist between dairy cattle, humans and rats at the onset of lactation.