Calcium-response factor (CaRF) is a unique DNA-binding protein first recognized as a transcription factor for its role in modulating transcription of the gene encoding Brain-Derived Neurotrophic Factor (BDNF) in neurons. Here I review evidence for the biological functions and transcriptional targets of CaRF in the brain and discuss potential mechanisms by which calcium-activated signaling pathways may modulate CaRF-dependent transcription. These data paint an emerging picture of CaRF as a regulatory nexus for signaling pathways that control aspects of synaptic development and neuronal function.