Pathfinding by growing axons in the developing or regenerating nervous system is guided by gradients of molecular guidance cues. The neuronal growth cone, located at the ends of axons, uses surface receptors to sense these cues and to transduce guidance information to cellular machinery that mediates growth and turning responses. Cytoplasmic Ca²⁺ signals have key roles in regulating this motility. Global growth cone Ca²⁺ signals can regulate cytoskeletal elements and membrane dynamics to control elongation, whereas Ca²⁺ signals localized to one side of the growth cone can cause asymmetric activation of effector enzymes to steer the growth cone. Modulating Ca²⁺ levels in the growth cone might overcome inhibitory signals that normally prevent regeneration in the central nervous system.