Calcium signaling in neurons as in other cell types mediates changes in gene expression, cell growth, development, survival, and cell death. However, neuronal Ca(2+) signaling processes have become adapted to modulate the function of other important pathways including axon outgrowth and changes in synaptic strength. Ca(2+) plays a key role as the trigger for fast neurotransmitter release. The ubiquitous Ca(2+) sensor calmodulin is involved in various aspects of neuronal regulation. The mechanisms by which changes in intracellular Ca(2+) concentration in neurons can bring about such diverse responses has, however, become a topic of widespread interest that has recently focused on the roles of specialized neuronal Ca(2+) sensors. In this article, we summarize synaptotagmins in neurotransmitter release, the neuronal roles of calmodulin, and the functional significance of the NCS and the CaBP/calneuron protein families of neuronal Ca(2+) sensors.