The Hippo pathway defined originally in Drosophila melanogaster is conserved in mammals. The fly core components Hippo, Sav, Wts, and Mats are conserved in mammals as Mst1/2, WW45, LATS1/2, and Mob1. The pathway impinges on transcriptional coactivator Yorkie in fly and YAP in mammals to coordinate cell proliferation and apoptosis. Several recent publications establish that the pathway is one major conserved mechanism governing cell contact inhibition, organ size control, and cancer development. This advance opens new vistas in exploring fundamental mechanisms in cell and developmental biology and offers potential targets to interfere with cancer development.