In this issue of Neuron, report the discovery of a new transcription factor, CaRF, that contributes to calcium stimulation of the BDNF gene through CaRE1, one of several calcium response elements found in the promoter of the BDNF gene. The CaRF/CaRE1 transcriptional pathway may control the expression of genes critical for activity-dependent, long-term changes in the central nervous system (CNS).