Liver diseases are leading causes of death and disability worldwide. Therefore, the development of new treatments for liver disease is urgent. An integral part of the treatment of any liver disease is the process of regeneration of its parenchyma. However, the current approach to studying mammalian liver regeneration is one-sided, focusing solely on the liver itself and neglecting its interactions with other organs. This includes organs of the functional excretory system, such as the lungs and kidneys, which can secrete factors, including HGF, EGF, TGFβ, IL6, and others, into the bloodstream, which influence reparative processes in the liver. Only a few studies exist in this area. However, without a systematic approach to studying liver regeneration, it is impossible to develop new and effective methods to stimulate its regeneration. This review presents data on the interaction of the regenerating liver with the nervous, endocrine, and immune systems, as well as with the lungs, kidneys, and intestines. © 2025 by the authors.