The recent identification of signaling elements that regulate skeletal muscle protein balance has provided the opportunity to determine how IGF-I alters these processes. Animal studies have revealed the important role of IGF-I in preventing muscle atrophy and enabled investigators to determine the hierarchy of signaling pathways and events within each pathway that are modulated by IGF-I. These discoveries provide opportunity for future studies to target these important signaling events and develop strategies to reverse loss of muscle mass that accompanies these catabolic states. Because there are no approved medical therapies that will reverse catabolism at present, this represents an opportunity to fulfill a major unmet medical need.