Skeletal muscle is the most abundant tissue in the human body and requires high levels of energy to function properly. It enables voluntary movement and body posture, relying on diverse fiber types, innervation, energy sources, and metabolic processes. Here, we summarize the contributions received at the time of publication of this Introductory Issue for the Special Issue entitled “Skeletal Muscle Atrophy: Cellular-Level Mechanisms.” The Special Issue is divided into three sections: the first focuses on skeletal muscle pathophysiology, the second on disease mechanisms, and the third on therapeutic development.