The interactions between organs play a crucial role in numerous physiological and pathological processes. In this context, liver is essential for maintaining homeostasis with other organs: many disorders can indeed originate from impaired organ-organ communication, resulting in concomitant pathological phenotypes. Hepatokines, proteins secreted by the liver, have been associated with diseases affecting various organs, including heart, muscles, bones and eyes. While both basic and clinical studies have proposed liver-centered interorgan communication, the regulatory mechanisms governing hepatokines production, secretion and reciprocal signaling with other organs remain unclear. Furthermore, more evidence is necessary to determine the involvement of additional hormones and cytokines in such communication. This chapter aims to summarize the current knowledge regarding interorgan communication within different diseases, emphasizing the potential role of hepatokines and other crucial signaling factors in acute gastrointestinal and pancreatic injury, offering an insight into the underlying functions and mechanisms of liver-mediated signal transduction and ultimately enhancing our disease understanding from an integrative perspective.