The chapter discusses the versatility and dynamics of calcium (Ca²⁺) signaling in cells, highlighting its role in regulating various cellular processes over a wide temporal range. Ca²⁺ signaling systems are assembled using an extensive toolkit of components, which can be mixed and matched to create diverse signaling units with different spatial and temporal properties. The balance between "on" reactions, which introduce Ca²⁺ into the cytoplasm, and "off" reactions, which remove it, determines the intracellular Ca²⁺ concentration. Ca²⁺ signaling is crucial for controlling gene expression patterns and is constantly remodeled in health and disease. The chapter also explores the spatial and temporal organization of Ca²⁺ signaling, including the formation of macromolecular complexes and the generation of Ca²⁺ waves. Additionally, it discusses the importance of Ca²⁺-dependent transcriptional regulation in maintaining cellular homeostasis and adapting to changes in Ca²⁺ signaling systems.The chapter discusses the versatility and dynamics of calcium (Ca²⁺) signaling in cells, highlighting its role in regulating various cellular processes over a wide temporal range. Ca²⁺ signaling systems are assembled using an extensive toolkit of components, which can be mixed and matched to create diverse signaling units with different spatial and temporal properties. The balance between "on" reactions, which introduce Ca²⁺ into the cytoplasm, and "off" reactions, which remove it, determines the intracellular Ca²⁺ concentration. Ca²⁺ signaling is crucial for controlling gene expression patterns and is constantly remodeled in health and disease. The chapter also explores the spatial and temporal organization of Ca²⁺ signaling, including the formation of macromolecular complexes and the generation of Ca²⁺ waves. Additionally, it discusses the importance of Ca²⁺-dependent transcriptional regulation in maintaining cellular homeostasis and adapting to changes in Ca²⁺ signaling systems.