Acromegaly results from growth hormone hypersecretion and is accompanied by deleterious changes in many tissues and organs. Some signs and symptoms of acromegaly respond to growth hormone-lowering therapy, but many are irreversible. Thus, early diagnosis and effective surgical, radiation, and medical therapies are the mainstays of combating this debilitating disease. Over the past several decades, the reestablishment of the transsphenoidal approach to pituitary surgery, the development of magnetic resonance imaging technology, refinements in the delivery of radiotherapy to pituitary tumors, and the development of long-acting somatostatin analogues have greatly improved our ability to effectively treat acromegaly. Advances in our understanding of hypothalamic-pituitary physiology, tumorigenesis, and tumor biology promise to further improve our ability to diagnose and treat patients with growth hormone-secreting pituitary tumors.