Acromegaly is a rare, chronic disorder in which the diagnosis is often delayed well into the course of the disease. It is associated with excess mortality, although the most accurate method of defining this is a topic of ongoing investigation. Serum growth hormone levels have proven to be the most reliable predictor of excess mortality with conflicting data surrounding IGF-1 levels. A host of potential confounding influences on mortality can be seen in patients with acromegaly including diabetes, sleep apnea, hypopituitarism, and the specific effects of specific treatment modalities, particularly radiotherapy. This chapter summarizes the current data regarding mortality in acromegaly.