In the brain, transcription factors are critical for linking external stimuli to protein production, enabling neurons and neuronal networks to adapt to the ever-changing landscape. Gene transcription and protein synthesis are also vital for the formation of long-term memory. Members of the myocyte enhancer factor-2 (MEF2) family of transcription factors have a well-characterized role in the development of a variety of tissues, but their role in the adult brain is only beginning to be understood. Recent evidence indicates that MEF2 regulates the structural and synaptic plasticity underlying memory formation. However, in stark contrast to most other transcription factors implicated in memory, MEF2-mediated transcription constrains (rather than promotes) memory formation. Here, we review recent data examining the role of MEF2 in adult memory formation in rodents.