The Hippo Pathway is a master regulatory network that regulates proliferation, cell growth, stemness, differentiation, and cell death. Coordination of these processes by the Hippo Pathway throughout development and in mature organisms in response to diverse external and internal cues plays a role in morphogenesis, in controlling organ size, and in maintaining organ homeostasis. Given the importance of these processes, the Hippo Pathway also plays an important role in organismal health and has been implicated in a variety of diseases including eye disease, cardiovascular disease, neurodegeneration, and cancer. This review will focus on Drosophila reports that identified the core components of the Hippo Pathway revealing specific downstream biological outputs of this complicated network. A brief description of mammalian reports will complement review of the Drosophila studies. This review will also survey upstream regulation of the core components with a focus on feedback mechanisms.