Extensive study of the E-proteins E2A and HEB duringlymphocyte development has revealed various functions for these bHLH transcription factors in regulating V(D)J recombination in both B- and T-cells. The study of E-proteins in mammals began with the identification of E2A by its ability to bind immunoglobulin heavy and light chain enhancers. Subsequent analysis has identified numerous roles for E2A and HEB at the immunoglobulin and T-cell receptor loci. E-protein targets also include the rag genes and other factors critical for recombination and for regulation of the developmental windows when cells undergo recombination. E-proteins appear to be master regulators that coordinate antigen receptor gene rearrangement and expression. This chapter focuses on how E-proteins regulate V(D)J recombination by activating transcription, initiating rearrangement and driving differentiation during B- and T-cell development.