The Hippo signaling pathway, first discovered in *Drosophila*, is a conserved regulator of organ size. The core of this pathway involves a kinase cascade from the tumor suppressor Hippo (Mst1 and Mst2 in mammals) to the oncoprotein Yorkie (Yki, YAP and TAZ in mammals), which regulates cell proliferation and survival. Recent studies have elucidated the molecular mechanisms and physiological functions of the Hippo signaling pathway in both *Drosophila* and mammals. The core kinase cascade integrates multiple upstream inputs, enabling dynamic regulation of tissue homeostasis in animal development and physiology. In *Drosophila*, the Kibra-Ex-Mer complex, which includes apical proteins, integrates signals from upstream receptors and downstream kinases. In mammals, the conservation of the core kinase cascade is evident, but additional complexity and divergence have been observed, such as the mechanism of YAP/TAZ inactivation and the role of RASSF family proteins. The pathway also plays crucial roles in various developmental contexts, including cell cycle exit, apoptosis, and cellular differentiation. Future research aims to identify the complete repertoire of upstream inputs and understand how different developmental pathways are integrated to specify organ size and shape.The Hippo signaling pathway, first discovered in *Drosophila*, is a conserved regulator of organ size. The core of this pathway involves a kinase cascade from the tumor suppressor Hippo (Mst1 and Mst2 in mammals) to the oncoprotein Yorkie (Yki, YAP and TAZ in mammals), which regulates cell proliferation and survival. Recent studies have elucidated the molecular mechanisms and physiological functions of the Hippo signaling pathway in both *Drosophila* and mammals. The core kinase cascade integrates multiple upstream inputs, enabling dynamic regulation of tissue homeostasis in animal development and physiology. In *Drosophila*, the Kibra-Ex-Mer complex, which includes apical proteins, integrates signals from upstream receptors and downstream kinases. In mammals, the conservation of the core kinase cascade is evident, but additional complexity and divergence have been observed, such as the mechanism of YAP/TAZ inactivation and the role of RASSF family proteins. The pathway also plays crucial roles in various developmental contexts, including cell cycle exit, apoptosis, and cellular differentiation. Future research aims to identify the complete repertoire of upstream inputs and understand how different developmental pathways are integrated to specify organ size and shape.