Calcium ion (Ca2+) is the only second messenger well recognized for the established biological role among various inorganic ions. When cellular Ca2+ controls diverse biological phenomena, it is regulated under exquisitely precise mechanisms. Many proteins have been identified as Ca2+ signal-regulating factors, and still new "players" are added to the repertory. In this review, we will focus on Ca2+ channels, Ca2+-binding proteins,and signaling pathways controlled by these Ca2+ signal-regulating proteins, in order to discuss on molecular bases, biological significance, and possible future developments of Ca2+ signaling.