Myokines are cytokines released from skeletal muscle tissue upon muscle contraction. Interleukin-6 (IL-6) was one of the first myokines identified through A-V differential blood samplings from exercising humans. Secretome analysis of human muscle cells revealed more than 300 potential myokines. Even among those identified, their actions are diverse: metabolic regulation, anti-inflammatory action, and muscle mass adaptation including regulation of regenerative processes. IL-6, myonectin, irisin, secreted protein acidic and rich in cysteine (SPARC), decorin, and adiponectin will be focused. Adaptive mechanism of skeletal muscle in response to strength training involving myokines is introduced. Because skeletal muscle tissue is not the only source of these myokines, and because they have multiple redundant roles, the overall picture of myokine regulation and their roles still needs to be investigated. They are definitely responsible for regulating the beneficial effect of exercise and physical activity on various organs and tissues.