Skeletal muscle is considered an essential tissue involved in many physiological functions such as metabolism, thermoregulation, respiration, and locomotion. It has become clear that genetic and environmental factors are intricately involved in regulating skeletal muscle volume or myofiber size. The complexity of the orchestration of the signaling pathways that regulate these factors is intriguing. Muscle biologists strive to elucidate the myriad of signaling interactions critical for muscle volume and homeostasis. In this topic, we aimed to gain new insights into the basis of muscle volumetric and homeostatic regulation. We collected nine papers that embody novel or important concepts to skeletal myology. The three main areas compose the manuscripts: adult myogenesis, skeletal muscle mass regulation, and cancer-induced muscle weakness.