<p>Activation of Ca²⁺ channels in Ca²⁺ stores in organelles and the plasma membrane generates cytoplasmic calcium ([Ca²⁺]_c) signals that control almost every aspect of cell function, including metabolism, vesicle fusion and contraction. Mitochondria have a high capacity for Ca²⁺ uptake and chelation, alongside efficient Ca²⁺ release mechanisms. Still, mitochondria do not store Ca²⁺ in a prolonged manner under physiological conditions and lack the capacity to generate global [Ca²⁺]_c signals. However, mitochondria take up Ca²⁺ at high local [Ca²⁺]_c signals that originate from neighbouring organelles, and also during sustained global elevations of [Ca²⁺]_c. Accumulated Ca²⁺ in the mitochondria stimulates oxidative metabolism and upon return to the cytoplasm, can produce spatially confined rises in [Ca²⁺]_c to exert control over processes that are sensitive to Ca²⁺. Thus, the mitochondrial handling of [Ca²⁺]_c is of physiological relevance. Furthermore, dysregulation of mitochondrial Ca²⁺ handling can contribute to debilitating diseases. We discuss the mechanisms and relevance of mitochondria in local and global calcium signals.</p>