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Written and edited by experts in the field, this collection from Cold Spring Harbor Perspectives in Biology provides a comprehensive update on all facets of calcium signaling. The contributors discuss the components and activities of the various calcium-sequestering organelles inside cells, the dynamic interactions that lead to spatiotemporally distinct signals in different circumstances, and the downstream effector mechanisms that translate the signals into biological outcomes. Recent advances in the field (e.g., structural insights into the functions of certain calcium channels) are emphasized throughout.