The myocyte enhancer factor-2 (MEF-2) family of transcription factors associate with co-repessors or co-activators to regulate development and function of T cells, neuronal cells, and muscle cells. Four family members, termed MEF-2A, -2B, -2C, and -2D, arise from alternatively spliced transcripts. These members bind as homo- and heterodimers to the MEF-2 site in the promoter region of affected genes. Differential regulation in the expression of the four transcripts implies functional distinction for each during embryogenesis and development. The process of differentiation from mesodermal precursor cells to myoblasts has led to the discovery of a variety of tissue-specific factors that regulate muscle gene expression. The myogenic basic helix-loop-helix proteins, including MyoD, myogenin, Myf-5, and MRF4, are one class of identified factors. The MEF-2 family represents a second class of DNA binding regulatory proteins. Each of these proteins binds to the MEF-2 target DNA sequence present in the regulatory regions of many muscle-specific genes.