Skeletal muscle, once viewed solely as a contractile apparatus, is now recognized as a secretory organ. It releases myokines and exerkines that influence distant organs such as the liver and adipose tissue. Conversely, the liver, renowned for its metabolic functions, serves as an endocrine entity, secreting hepatokines that facilitate bidirectional communication with skeletal muscle and other tissues. Dysregulation of this network can lead to adverse outcomes. Sarcopenia is a prominent example. In this chapter, we will explore the intricate interplay between skeletal muscle tissue and the liver, elucidating the central role of inter-organ communication in maintaining homeostatic equilibrium.