The semaphorin family comprises secreted and transmembrane signaling proteins that function in the nervous, immune, respiratory and cardiovascular systems. Sema3A, a secreted type of semaphorin, is now recognized as the most potent repulsive molecule inhibiting or repelling neurite outgrowth. The biological actions of Sema3A are mediated via neuropilin (an)-l, a receptor or one of the components of a receptor complex for Sema3A. Although the molecular mechanisms of Sema3A-an-1 signaling are largely unknown, a pertussis toxin-sensitive trimeric G protein (s), Rae-1, collapsin response mediator protein (CRMP), cyclic nucleotides and tyrosine kinase (s) have been implicated as essential and/or modulatory components of these processes. As repulsive molecules could be impediments to axon outgrowth, determining how these repulsive molecules exert their actions has the potential of uncovering new therapeutic approaches to injury and/or degeneration of neuronal tissues.