Ca(2+) signals have profound and varied effects on growth cone motility and guidance. Modulation of Ca(2+) influx and release from stores by guidance cues shapes Ca(2+) signals, which determine the activation of downstream targets. Although the precise molecular mechanisms that underlie distinct Ca(2+)-mediated effects on growth cone behaviours remain unclear, recent studies have identified important players in both the regulation and targets of Ca(2+) signals in growth cones.