Calcium has long been recognized as a key player in the control of axonal growth and guidance. Recent studies lend support to this pivotal role by showing that local changes in calcium can directly induce the formation of filopodia in vivo and turn a growth cone in vitro. Under normal growth conditions, the L1 adhesion molecule has now been shown to induce local rather than global changes in calcium in growth cones, and this suggests that cell adhesion molecules (CAMs) use localized calcium transients to stimulate axonal growth and guidance. A number of recent reports have demonstrated that the neurite outgrowth response stimulated by L1 and other adhesion molecules (NCAM, N-cadherin, laminin) also depends in part upon the integrity of the MAPK cascade in cells. In this review we consider the recent data and suggest that calcium and the MAPK cascade might be required for very distinct growth cone functions. Finally, we will consider the contentious issue of how the above CAMs activate signaling cascades in growth cones and review the recently available data that support the hypothesis that at least one of these CAMs (N-cadherin) might promote growth cone motility by directly interacting with the FGFR in growth cones.