The Hippo pathway, initially identified in *Drosophila melanogaster* screens for tissue growth regulation, has been extensively studied in both *Drosophila* and mammals. The core of the Hippo pathway involves a kinase cascade, transcriptional coactivators, and DNA-binding partners. Recent studies have expanded this pathway to include over 30 components, forming a complex signaling network. The pathway is regulated by intrinsic cell mechanisms, such as cell-cell contact, cell polarity, and actin cytoskeleton, as well as extrinsic signals like cellular energy status, mechanical cues, and hormonal signals acting through G-protein-coupled receptors (GPCRs). The major functions of the Hippo pathway include restricting tissue growth in adults and modulating cell proliferation, differentiation, and migration in developing organs. Dysregulation of the Hippo pathway leads to aberrant cell growth and neoplasia. This review focuses on recent advancements in understanding the molecular actions of the core Hippo kinase cascade and discusses key open questions in the regulation and function of the Hippo pathway. The core kinase cascade of the Hippo pathway involves the activation of LATS1/2 by MST1/2, which in turn phosphorylate and inactivate YAP and TAZ, leading to their cytoplasmic retention and degradation. The pathway is regulated by various upstream signals, including physical cues, soluble factors, and stress signals, which modulate the phosphorylation events of the core kinase cascade through peripheral components. The regulation of the Hippo pathway by GPCRs is a universal response to hormonal cues, and the pathway also interacts with other signaling pathways like Wnt, BMP, Notch, and Hedgehog. The spatial regulation of MST and LATS, as well as the post-translational regulation of LATS1/2, are also discussed. The transcriptional programs of YAP/TAZ and their functional outputs, including tissue progenitor cell self-renewal and expansion, are highlighted.The Hippo pathway, initially identified in *Drosophila melanogaster* screens for tissue growth regulation, has been extensively studied in both *Drosophila* and mammals. The core of the Hippo pathway involves a kinase cascade, transcriptional coactivators, and DNA-binding partners. Recent studies have expanded this pathway to include over 30 components, forming a complex signaling network. The pathway is regulated by intrinsic cell mechanisms, such as cell-cell contact, cell polarity, and actin cytoskeleton, as well as extrinsic signals like cellular energy status, mechanical cues, and hormonal signals acting through G-protein-coupled receptors (GPCRs). The major functions of the Hippo pathway include restricting tissue growth in adults and modulating cell proliferation, differentiation, and migration in developing organs. Dysregulation of the Hippo pathway leads to aberrant cell growth and neoplasia. This review focuses on recent advancements in understanding the molecular actions of the core Hippo kinase cascade and discusses key open questions in the regulation and function of the Hippo pathway. The core kinase cascade of the Hippo pathway involves the activation of LATS1/2 by MST1/2, which in turn phosphorylate and inactivate YAP and TAZ, leading to their cytoplasmic retention and degradation. The pathway is regulated by various upstream signals, including physical cues, soluble factors, and stress signals, which modulate the phosphorylation events of the core kinase cascade through peripheral components. The regulation of the Hippo pathway by GPCRs is a universal response to hormonal cues, and the pathway also interacts with other signaling pathways like Wnt, BMP, Notch, and Hedgehog. The spatial regulation of MST and LATS, as well as the post-translational regulation of LATS1/2, are also discussed. The transcriptional programs of YAP/TAZ and their functional outputs, including tissue progenitor cell self-renewal and expansion, are highlighted.