Individual striated muscle fibers communicate in both a paracrine and endocrine fashion and are also involved in the crosstalk with other tissues and organs such as the adipose tissue, immune system, liver, pancreas, bones, and brain (Delezie andHandschin, 2018). The striatedmuscle, which accounts for 40% of bodymass, presents high biosynthetic activity, and extensive vascularization, features that endorse current thinking that muscle is the largest endocrine system of the body (Benatti and Pedersen, 2015). There are hundreds of muscle secretory products, collectively known as myokines, including proteins, miRNA, and exosomes (Barone et al., 2016). Muscle secretion is significantly affected by muscle contraction (Son et al., 2018) due to the activation of mechanotransduction pathways (Coletti et al., 2016a). It has been suggested that the adipose tissue is also an endocrine organ, producing adipokines- leptin, and other hormones, in addition to cytokines (Galic et al., 2010). The inflammatory infiltrate in fat depots affects the course of several diseases, including cancer (Batista et al., 2012; Sawicka and Krasowska, 2016; Neto et al., 2018; Opatrilova et al., 2018), and an extensive review on the role of adipokines in disease has been published elsewhere (Orzechowski et al., 2014). Myokines, adipokines, and cytokines are major therapeutic targets in both muscular and non-muscular diseases (Lindegaard et al., 2013;Manole et al., 2018), and understanding of their role in tissue crosstalk represents a subject of great interest in current biology.We have therefore chosen to address this paradigm within this Frontiers special issue on “Myokines, Adipokines, Cytokines in Muscle Pathophysiology.”