Calcium is the most abundant mineral in human body with 99% deposit in bone. The intestinal absorption, kidney reabsorption and bone resorption are three major events for calcium homeostasis regulated by CaSR through a series of complicated mechanisms. Any miscommunication of these processes can lead to diseases associated with dysfunctional regulation of calcium. In addition, calcium in diets and supplements along with vitamin D play critical roles in calcium homeostasis. Low calcium intake or low vitamin D level can also result in bone diseases. High calcium intake can reduce the risk of breast cancer and contribute to the reduced rate of bone loss and fracture incidence in elders. On the other hand, although high calcium intake can reduce the risk of many diseases, it also can increase the risks of acute gastrointestinal events, kidney stone, and cardiovascular diseases such as myocardial infarction and stroke. Therefore, the consumption and supplementation of calcium should abide by the health status of individuals.