Published 2019. This article is a U.S. Government work and is in the public domain in the USA Myokines are molecules produced and secreted by skeletal muscle to act in an auto-, para- and endocrine manner to alter physiological function of target tissues. The growing number of effects of myokines on metabolism of distant tissues provides a compelling case for crosstalk between skeletal muscle and other tissues and organs to regulate metabolic homoeostasis. In this review, we summarize and discuss the current knowledge regarding the impact on metabolism of several canonical and recently identified myokines. We focus specifically on myostatin, β-aminoisobutyric acid, interleukin-15, meteorin-like and myonectin, and discuss how these myokines are induced and regulated as well as their overall function. We also review how these myokines may serve as potential prognostic biomarkers that reflect whole-body metabolism and how they may be attractive therapeutic targets for treating muscle and metabolic diseases.