Summary: Calcium is one of the most important minerals in the human body. All multidirectional biological functions of calcium are fully expressed already in the prenatal period, while a similar wide-range spectrum of actions continues throughout the subsequent stages of life, being controlled by endocrine mechanisms. Although only 1% of the systemic calcium resources is expressed as the ionized form in both the intra- and extracellular fluid, a number of important functions are attributed to this compartment, including the roles of enzyme activator, secondary messenger (protein kinases), transmission of bioelectrical impulses in all cells, neurotransmission, myocyte activity and muscle contraction, hormonal and exocrine secretion, regulation of blood coagulation, and also in immunomodulation, inflammation, tissue proliferation and regeneration. The remaining systemic calcium reserves, i.e. 99% of the total content, are deposited in a mineral form (hydroxyapatite or calcium hydroxyphosphate) bonded in the skeleton, teeth and connective tissue. Noticeably, this skeletal calcium – essentially responsible for bone mineral mass and bone structure – can also be replaceable under some conditions, mainly through the processes of resorption and formation, and if disturbed, it leads to disturbances of calcium homeostasis and reduction of bone mineral density. The present review article, which resulted from a cooperative panel of multidisciplinary clinicians, summarizes the current state of knowledge about the physiological role of calcium in key systems and organs, and also briefly discusses recommended intakes, therapeutic effects in selected chronic cardiovascular, excretory system, endocrine and rheumatic diseases and supplementation guidelines in relation to sex and age, with particular emphasis on the periods of childhood and adolescence, pregnancy and lactation and the old age.