Skeletal muscle has only recently been considered a secretory organ. Muscle-derived proteins are now termed myokines. Until date, about 20 proteins known as cytokines, growth factors, and adipokines have been reported as myokines. However, only a few studies have been able to demonstrate secretion from the skeletal muscle. Furthermore, many reports are still uncertain of whether proteins are secreted from skeletal muscle cells or from the surrounding tissue, because some studies have measured myokine concentration in blood taken from human and animal subjects, which also contains other organ-derived proteins. Secretion of some myokines is promoted by muscle contraction or insulin stimulation, whereas others seem to be constitutively secreted. The mechanisms of action and roles of myokines are also complicated. Some are believed to affect distant organs through endocrine and paracrine mechanisms, while others affect organs through an autocrine mechanism. In this article, we review updates of myokines, including their history. Furthermore, the article discusses the need to re-define myokines in order to avoid possible misunderstandings because of insufficient data.