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The loss of lean body mass (muscle wasting) is initiated by cascades or events that precipitate increased proteolysis. Muscle wasting is stimulated by internal and external factors. Humorally related feedback loops stimulated by disease states, e.g., cancer, inflammatory myopathies, leukemia, or sepsis, and initiated as a response to systemic inflammatory response syndrome can cause a downward progression of events, resulting in chronic illness or even death. This article discusses the pathogenesis of muscle wasting, which is often referred to as cachexia.