This chapter summarizes the distribution and physiological roles assumed by calcium ion. A description of fundamental physicochemical and structural properties provides a backdrop to a discussion of the relevance of the cation and a better understanding of its physiological chemistry. Following an introduction of the basic structural and coordination chemistry of protein-bound calcium, there is an overview of cellular uptake of calcium from the diet into serum and cells, the chemistry blood proteins and processes such as blood clotting, intracellular calcium transport, storage and regulation, and the mechanisms of membrane transporters. The role of calcium as a secondary messenger and in neural signalling is also developed, as well as general sensing, buffering and other control mechanisms (cellular homeostasis). A general comparison is made with homologous calcium proteins from prokaryotes and the chemistry of excreted ionophores as antibacterials is outlined. A final closing section details many of the interesting and important questions that remain to be addressed in cellular calcium chemistry.