Striated skeletal is subject to nonlethal cycles of atrophy in response to a variety of physiological and pathological stimuli, including: starvation, disuse, denervation and inflammation. These cells can also undergo cell death in response to appropriate developmental signals or specific pathological insults. Most of the insights gained into the control of vertebrate skeletal muscle atrophy and death have resulted from experimental interventions rather than natural processes. In contrast, the intersegmental muscles (ISMs) of moths are giant cells that initiate sequential and distinct programs of atrophy and death at the end of metamorphosis as a normal component of development. This model has provided fundamental information about the control, biochemistry, molecular biology and anatomy of naturally occurring atrophy and death in vivo. The ISMs have provided a good complement to studies in vertebrates and may provide insights into clinically relevant disorders.