Helix–loop–helix proteins are essential factors for lymphocyte development and function. In particular, E-proteins are crucial for commitment of lymphoid progenitors to the B-and T-cell lineages. E-proteins are negatively regulated by the Id class of helix–loop–helix proteins. The Id proteins function as dominant-negative inhibitors of E-proteins by inhibiting their ability to bind DNA. Here, we review the role of E-proteins and their Id protein antagonists in lymphocyte proliferation and developmental progression. In addition, we discuss how E-protein activity and Id gene expression are regulated by T-cell receptor (TCR) and pre-TCR-mediated signalling.