Acromegaly is generally caused by growth hormone (GH) hypersecretion from a benign, monoclonal pituitary adenoma. As in other neoplastic conditions, pituitary tumor formation and dysregulated hormone secretion are most likely the ultimate result of a series of genetic alterations. A number of molecular and biochemical defects have been associated with pituitary tumorigenesis. Molecular events such as tumor suppressor gene inactivation and oncogene activation involved in pituitary tumor progression are examined. The role of hypothalamic regulatory hormones and hereditary syndromes involving acromegaly are also discussed.