The control of organ size growth is one of the most fundamental aspects of life. In the past two decades, a highly conserved Hippo signaling pathway has been identified as a key molecular mechanism for governing organ size regulation. In the middle of this pathway is a kinase cascade that negatively regulates the downstream component Yes-associated protein (YAP)/transcriptional coactivator with PDZ-binding motif (TAZ)/Yorkie through phosphorylation. Phosphorylation of YAP/TAZ/Yorkie promotes its cytoplasmic localization, leads to cell apoptosis and restricts organ size overgrowth. When the Hippo pathway is inactivated, YAP/TAZ/Yorkie translocates into the nucleus to bind to the transcription enhancer factor (TEAD/TEF) family of transcriptional factors to promote cell growth and proliferation. In this review, we will focus on the structural and functional studies on the downstream transcription factor TEAD and its coactivator YAP.