Proper control of Ca(2+) signaling is mandatory for effective cell migration, which is critical for embryonic development, wound healing, and cancer metastasis. However, how Ca(2+) coordinates structural components and signaling molecules for proper cell motility had remained elusive. With the advance of fluorescent live-cell Ca(2+) imaging in recent years, we gradually understand how Ca(2+) is regulated spatially and temporally in migrating cells, driving polarization, protrusion, retraction, and adhesion at the right place and right time. Here we give an overview about how cells create local Ca(2+) pulses near the leading edge, maintain cytosolic Ca(2+) gradient from back to front, and restore Ca(2+) depletion for persistent cell motility. Differential roles of Ca(2+) in regulating various effectors and the interaction of roles of Ca(2+) signaling with other pathways during migration are also discussed. Such information might suggest a new direction to control cancer metastasis by manipulating Ca(2+) and its associating signaling molecules in a judicious manner.