Publisher Summary This chapter focuses on the receptor-activated Ca 2+ signaling processes and on the mechanism by which receptor activation leads to the entry of Ca 2+ into cells across the plasma membrane. The chapter presents a particular theory termed “capacitative model” for the mechanism by which the entry of Ca 2+ is regulated by agonists acting through the phosphoinositide system. It is now quite well established that the initial, agonist-induced [Ca 2+ ] i signal in such cells is derived from the Ca 2+ -releasing actions of (1,4,5)IP 3 on an intracellular Ca 2+ sequestering organelle. However, in virtually all cells that utilize this mechanism, the initial release of intracellular Ca 2+ is followed or accompanied by an accelerated entry of Ca 2+ into the cytoplasm across the plasma membrane; mechanism by which this process is regulated has been somewhat more elusive and may vary in different cellular systems. Further investigation of this interesting aspect of the Ca 2+ - phosphoinositide system provides with many additional discoveries and surprises in the near future.