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Skeletal muscle is the largest organ in the body. Skeletal muscles are primarily characterized by their mechanical activity required for posture, movement, and breathing, which depends on muscle fiber contractions. However, skeletal muscle is not just a component in our locomotor system, but has been identified as a secretory organ. Cytokines and other peptides that are produced, expressed, and released by muscle fibers and exert either autocrine, paracrine, or endocrine effects that are classified as “myokines.” The muscle secretome consists of several hundred secreted peptides. This finding provides a conceptual basis and a paradigm for understanding how muscles communicate with other organs such as adipose tissue, liver, pancreas, bones, and brain. In addition, several myokines exert their effects within the muscle itself and some myokines have been identified as having an anticancer effect. Many proteins produced by skeletal muscle are dependent upon contraction. Therefore, it is likely that myokines may contribute to mediate the health benefits of exercise.Skeletal muscle is the largest organ in the body. Skeletal muscles are primarily characterized by their mechanical activity required for posture, movement, and breathing, which depends on muscle fiber contractions. However, skeletal muscle is not just a component in our locomotor system, but has been identified as a secretory organ. Cytokines and other peptides that are produced, expressed, and released by muscle fibers and exert either autocrine, paracrine, or endocrine effects that are classified as “myokines.” The muscle secretome consists of several hundred secreted peptides. This finding provides a conceptual basis and a paradigm for understanding how muscles communicate with other organs such as adipose tissue, liver, pancreas, bones, and brain. In addition, several myokines exert their effects within the muscle itself and some myokines have been identified as having an anticancer effect. Many proteins produced by skeletal muscle are dependent upon contraction. Therefore, it is likely that myokines may contribute to mediate the health benefits of exercise.