Regular physical activity not only improves the exercise capacity of the skeletal muscle performing the contractions, but it is beneficial for the whole body. An extensive search for “exercise factors” mediating these beneficial effects has been going on for decades. Particularly skeletal muscle tissue has been investigated as a source of circulating exercise factors, and several myokines have been identified. However, exercise also has an impact on other tissues. The liver is interposed between energy storing and energy utilising tissues and is highly active during exercise, maintaining energy homeostasis. Recently, a novel group of exercise factors—termed hepatokines—has emerged. These proteins (fibroblast growth factor 21, follistatin, angiopoietin-like protein 4, heat shock protein 72, insulin-like growth factor binding protein 1) are released from the liver and increased in the bloodstream during or in the recovery after an exercise bout. In this narrative review, we evaluate this new group of exercise factors focusing on the regulation and potential function in exercise metabolism and adaptations. These hepatokines may convey some of the beneficial whole-body effects of exercise that could ameliorate metabolic diseases, such as obesity or type 2 diabetes.