In the last years, scientists have shown that skeletal muscle is not a pure locomotor unit or responsible for propulsion and posture. Skeletal muscle encompasses one of the major organs of the body (constituting about 40% of the body mass in non-obese men). It regulates energy and metabolic processes and is now recognized as an organ capable of producing molecules with vital functions. These molecules are termed myokines, a new field of research in the health sciences, and represent an open field of discoveries and applications in several areas. The aim of this review was to show the role of some well-known myokines in the maintenance of homeostasis. Our search was performed in databases such as Medline/Pubmed, Embase and Scielo. Some relevant myokines are interleukin-6 (IL-6), IL-8, IL-15, irisin, myostatin, fibroblast growth factor 21 (FGF21), leukemia inhibitory factor (LIF), brain-derived neurotrophic factor (BDNF), and insulin-like growth factor-1 (IGF-1). They are related to play a positive or negative role in muscle function and metabolism homeostasis. They are associated with the regulation of glucose and lipid metabolism, the deposition of fat in the adipose tissue, and the "browning" of the white adipose tissue. For these reasons, they can interfere with the prevention of obesity, diabetes, metabolic syndrome, and cardiovascular diseases. The discovery of the myokines has opened a new direction in understanding the effects of exercises on humans.