The capacity to remember our past experiences and organize our future draws on a number of cognitive processes that allow our brain to form and store neural representations that can be recalled and updated at will. In the brain, these processes require mechanisms of neural plasticity in the activated circuits, brought about by cellular and molecular changes within the neurons activated during learning. At the cellular level, a wealth of experimental data accumulated in recent years provides evidence that signaling from synapses to nucleus and the rapid regulation of the expression of immediate early genes encoding inducible, regulatory transcription factors is a key step in the mechanisms underlying synaptic plasticity and the modification of neural networks required for the laying down of memories. In the activated neurons, these transcriptional events are thought to mediate the activation of selective gene programs and subsequent synthesis of proteins, leading to stable functional and structural remodeling of the activated networks, so that the memory can later be reactivated upon recall. Over the past few decades, novel insights have been gained in identifying key transcriptional regulators that can control the genomic response of synaptically activated neurons. Here, as an example of this approach, we focus on one such activity-dependent transcription factor, Zif268, known to be implicated in neuronal plasticity and memory formation. We summarize current knowledge about the regulation and function of Zif268 in different types of brain plasticity and memory processes.