Ion channels and receptors are the structural basis for neural signaling and transmission. Recently, the function of ion channels and receptors has been demonstrated to be modulated by many intracellular and extracellular chemicals and signaling molecules. Increasing evidence indicates that the complexity and plasticity of the function of central nervous system is determined by the modulation of ion channels and receptors. Among various mechanisms, Ca 2+ signaling pathways play important roles in neuronal activity and some pathological changes. Ca 2+ influx through ion channels and receptors can modulate its further influx in a feedback way or modulate other ion channels and receptors. The common feature of the modulation is that Ca 2+ /calmodulin (CaM) is the universal mediator. CaM maintains the coordination among ion channels/receptors and intracellular Ca 2+ homeostasis by feedback modulation of ion channels/receptors activity. This review focuses on the modulating processes of ion channels and receptors mediated by CaM, and further elucidates the mechanisms of Ca 2+ signaling.