The myocyte enhancer factor 2 (MEF2) transcription factors were originally identified, as their family name implies, on the basis of their role in muscle differentiation. Expression of the four MEF2 proteins, however, is not restricted to contractile tissue. While it has been known for more than a decade that MEF2s are abundantly expressed in neurons, their contributions to the development and function of the nervous system are only now being elucidated. Interestingly, the emerging mechanisms regulating MEF2 in neurons have significant parallels with the regulatory mechanisms in muscle, despite the quite distinct identities of these two electrically excitable tissues. The goal of this chapter is to provide an introduction to those regulatory mechanisms and their consequences for brain development. As such, we first provide an overview of MEF2 itself and its expression within the central nervous system. The second part of this chapter describes the signaling molecules that regulate MEF2 transcriptional activity and their contributions to MEF2 function. The third part of this chapter discusses the role of MEF2 proteins in the developing nervous system and compares the analogous functions of this protein family in muscle and brain.