The Hippo signaling pathway is a central mechanism in multicellular organisms that integrates various mechanical, biochemical, and stress cues to regulate cell proliferation, survival, differentiation, and mechanics, thereby controlling organ development, homeostasis, and regeneration. The pathway is highly conserved from *Drosophila* to mammals and involves a core kinase cascade targeting Yes-associated protein (YAP)/transcriptional co-activator with PDZ-binding motif (TAZ) to modulate gene expression. Key components include MST1/2 (Hippo kinases), LATS1/2 (kinase inhibitors), SAV1 (scaffolding protein), MOB1A/B, NF2, and WWC1-3 ( adaptor proteins). YAP/TAZ, the major downstream effectors, regulate cell proliferation, survival, and differentiation through interactions with TEAD1-4. The pathway is regulated by diverse upstream signals, including biophysical, biochemical, metabolic, and stress cues, and exhibits feedback mechanisms to maintain homeostasis. In development, the Hippo pathway plays crucial roles in cell fate decisions, tissue morphogenesis, and organ size regulation. For example, in the liver, YAP/TAZ promotes cholangiocyte differentiation and inhibits hepatocyte differentiation. In the intestine, YAP/TAZ has pro-proliferation and anti-differentiation roles in stem cells. In the heart, YAP/TAZ is essential for cardiomyocyte proliferation and epicardium development. In the brain, YAP/TAZ induce NPC proliferation and promote astrocytic differentiation. The Hippo pathway also regulates the development of other organs, such as the lungs, pancreas, skeletal muscle, skin, breasts, and eyes. Understanding the molecular organization and regulatory mechanisms of the Hippo pathway holds promise for developing novel therapeutics in regenerative medicine.The Hippo signaling pathway is a central mechanism in multicellular organisms that integrates various mechanical, biochemical, and stress cues to regulate cell proliferation, survival, differentiation, and mechanics, thereby controlling organ development, homeostasis, and regeneration. The pathway is highly conserved from *Drosophila* to mammals and involves a core kinase cascade targeting Yes-associated protein (YAP)/transcriptional co-activator with PDZ-binding motif (TAZ) to modulate gene expression. Key components include MST1/2 (Hippo kinases), LATS1/2 (kinase inhibitors), SAV1 (scaffolding protein), MOB1A/B, NF2, and WWC1-3 ( adaptor proteins). YAP/TAZ, the major downstream effectors, regulate cell proliferation, survival, and differentiation through interactions with TEAD1-4. The pathway is regulated by diverse upstream signals, including biophysical, biochemical, metabolic, and stress cues, and exhibits feedback mechanisms to maintain homeostasis. In development, the Hippo pathway plays crucial roles in cell fate decisions, tissue morphogenesis, and organ size regulation. For example, in the liver, YAP/TAZ promotes cholangiocyte differentiation and inhibits hepatocyte differentiation. In the intestine, YAP/TAZ has pro-proliferation and anti-differentiation roles in stem cells. In the heart, YAP/TAZ is essential for cardiomyocyte proliferation and epicardium development. In the brain, YAP/TAZ induce NPC proliferation and promote astrocytic differentiation. The Hippo pathway also regulates the development of other organs, such as the lungs, pancreas, skeletal muscle, skin, breasts, and eyes. Understanding the molecular organization and regulatory mechanisms of the Hippo pathway holds promise for developing novel therapeutics in regenerative medicine.