Developmental defects in the cardiac outflow tract (OFT) cause many common human congenital heart diseases, including DiGeorge syndrome. Tbx1, a T-box transcription factor, is involved in the pathogenesis of this syndrome but a specific role for Tbx1 in OFT morphogenesis has not been established. Now, Xu et al. show that Tbx1 has a dual role in OFT development (see p. 3217). By studying genetically modified and conditional mouse mutants of Tbx1, the researchers show that correct separation of the aorta and pulmonary arteries in the OFT requires Tbx1 function. This function also regulates OFT growth by supporting cell proliferation in the secondary heart field (SHF) – the source of cells that form the OFT. This is the first indication that a genetic defect related to human congenital heart disease directly affects SHF function and suggests that SHF malfunction may underlie other heart defects.