Gene transcription is the process by which the genetic codes of organisms are read and interpreted as a set of instructions for cells to divide, differentiate, migrate, and mature. As cells function in their respective niches, transcription further allows mature cells to interact dynamically with their external environment while reliably retaining fundamental information about past experiences. In this Review, we provide an overview of the field of activity-dependent transcription in the vertebrate brain and highlight contemporary work that ranges from studies of activity-dependent chromatin modifications to plasticity mechanisms underlying adaptive behaviors. We identify key gaps in knowledge and propose integrated approaches toward a deeper understanding of how activity-dependent transcription promotes the refinement and plasticity of neural circuits for cognitive function.