Individual transcription factors in the brain frequently display broad functional versatility, thereby controlling multiple cellular outputs. In accordance, neuron-restricted mutagenesis of the murine Srf gene, encoding the transcription factor serum response factor (SRF), revealed numerous SRF functions in the nervous system. First, SRF controls immediate early gene (IEG) activation associated with perception of synaptic activity, learning and memory. Second, processes linked to actin cytoskeletal dynamics are mediated by SRF, such as developmental neuronal migration, outgrowth and pathfinding of neurites, as well as synaptic targeting. Therefore, SRF seems to be instrumental in converting synaptic activity into plasticity-associated structural changes in neuronal connectivities. This highlights the decisive role of SRF in integrating cytoskeletal actin dynamics and nuclear gene expression. Finally, we relate SRF to the multi-functional transcription factor CREB and point out overlapping, distinct and concerted functions of these two transcriptional regulators in the brain.