Calcium, phosphate and magnesium are essential for human function and life. Each electrolyte is readily found in the human diet, and homeostasis is tightly regulated by the intestine, kidney and bone as well as other critical hormones, receptors and transporters. Disturbance to this balance can result in symptomatic disease and life-threatening manifestations. Calcium and phosphate are particularly co-dependent with disruption to the balance of one often influencing the other. It is important that clinicians have a thorough understanding of the mechanisms underplaying the homeostasis of each electrolyte as they have implications for prevention and management of disease. This chapter aims to outline the importance of calcium, phosphate and magnesium; the regulation of each electrolyte and the consequences of imbalance.