Ca2+ entry into neurons is one of the major effectors of stimulus-induced physiological change. Ca2+ can enter neurons through a number of different voltage-gated and ligand-gated channels. Depending on the route of entry, Ca2+ stimulates distinct intracellular signaling pathways, which activate different sets of genes, resulting in alternative physiological outcomes for the cell. These recent results suggest that the specific effect of a single biochemical second messenger can vary as a consequence of its route of entry into the cell.