The control of organ size is a basic biological question. In the past several years, the Hippo signaling pathway has been delineated and shown to be crucial in control of organ size in both Drosophila and mammals. Acting downstream of the Hippo pathway is the Yki/YAP/TAZ transcription co-activators. In mammalian cells, the Hippo pathway kinase cascade inhibits YAP and its paralog TAZ by phosphorylation and promotion of their cytoplasmic localization. The TEAD family transcription factors have recently been identified as evolutionarily conserved key mediators of YAP biological functions. yap is a candidate oncogene, and several other components of the Hippo pathway are tumor suppressors. Dysregulation of the Hippo pathway contributes to the loss of contact inhibition observed in cancer cells. Therefore, the Hippo-YAP pathway connects the regulation of organ size and tumorigenesis.