Cleft palate, a malformation of the secondary palate development, is one of the most common human congenital birth defects. Palate formation is a complex process resulting in the separation of the oral and nasal cavities that involves multiple events, including palatal growth, elevation, and fusion. Recent findings show that transforming growth factor beta (TGF-β) signaling plays crucial roles in regulating palate development in both the palatal epithelium and mesenchyme. Here, we highlight recent advances in our understanding of TGF-β signaling during palate development.