The Hippo pathway is a conserved signaling pathway essential for regulating organ growth in Drosophila and vertebrates. While the core kinases Hippo/Mst and Warts/Lats are well understood, the upstream inputs and downstream outputs of the pathway remain less clear. Recent studies have revealed new insights into the dynamic regulation of Hippo signaling during development, highlighting its expanding roles in growth control and regeneration. The pathway is involved in regulating cell proliferation and apoptosis, and its dysregulation is linked to various cancers. In Drosophila, loss of Hippo signaling leads to overgrowth of imaginal discs and adult structures, while in mammals, it plays a crucial role in liver size regulation. The Hippo pathway consists of a core kinase cascade with multiple transcriptional outputs, and its activity is regulated by various upstream inputs, including cell polarity determinants such as Crumbs, Expanded/Merlin/Kibra, and Lethal giant larvae. These components interact with the core Hippo pathway to modulate its activity, influencing organ growth and tissue size. The Hippo pathway also interacts with other signaling pathways, such as those involved in cell polarity and regeneration, to regulate organ size and cell cycle exit. In mammals, the Hippo pathway is involved in maintaining organ size and preventing excessive growth, but its role in different tissues may vary. The regulation of the Hippo pathway is complex and involves multiple inputs, including cell-cell contacts, extracellular cues, and stress signals. Understanding the regulation of the Hippo pathway is crucial for elucidating the mechanisms that control organ growth and regeneration in both Drosophila and mammals.The Hippo pathway is a conserved signaling pathway essential for regulating organ growth in Drosophila and vertebrates. While the core kinases Hippo/Mst and Warts/Lats are well understood, the upstream inputs and downstream outputs of the pathway remain less clear. Recent studies have revealed new insights into the dynamic regulation of Hippo signaling during development, highlighting its expanding roles in growth control and regeneration. The pathway is involved in regulating cell proliferation and apoptosis, and its dysregulation is linked to various cancers. In Drosophila, loss of Hippo signaling leads to overgrowth of imaginal discs and adult structures, while in mammals, it plays a crucial role in liver size regulation. The Hippo pathway consists of a core kinase cascade with multiple transcriptional outputs, and its activity is regulated by various upstream inputs, including cell polarity determinants such as Crumbs, Expanded/Merlin/Kibra, and Lethal giant larvae. These components interact with the core Hippo pathway to modulate its activity, influencing organ growth and tissue size. The Hippo pathway also interacts with other signaling pathways, such as those involved in cell polarity and regeneration, to regulate organ size and cell cycle exit. In mammals, the Hippo pathway is involved in maintaining organ size and preventing excessive growth, but its role in different tissues may vary. The regulation of the Hippo pathway is complex and involves multiple inputs, including cell-cell contacts, extracellular cues, and stress signals. Understanding the regulation of the Hippo pathway is crucial for elucidating the mechanisms that control organ growth and regeneration in both Drosophila and mammals.