The Hippo pathway was first discovered in Drosopliha melanogaster; orthologs are also present in mammals. The core kinase cassette of this pathway is highly conserved in all species and inhibits downstream effectors that are involved in organ size regulation, stem cell self-renewal, tissue regeneration, DNA damage response, senescence, cell metabolism, and cancer development. Hippo cross talks with many other pathways. This is a complex network, and deciphering of the key nodes might hold great promise for both regenerative medicine and cancer treatment.