During development of the nervous system, cell adhesion molecules (CAMs) promote cell migration and axonal growth; yet, at other times, CAMs inhibit these events by maintaining stable adhesion between cells. In the present review, we consider recent results that help to explain the paradoxical findings that individual CAMs can both promote and inhibit neuronal plasticity. In particular, we discuss the accumulating evidence that axonal growth stimulated by CAMs depends upon the activation of a second messenger pathway that culminates in calcium entry into neurons rather than on adhesion per se.