The majority of patients with acromegaly harbor a functioning growth hormone (GH) pituitary adenoma. Growth hormone–secreting adenomas correspond to about 20% of all pituitary adenomas. From the histopathological point of view, a variety of adenomas may present with clinical signs and symptoms of GH hypersecretion including pure GH cell adenomas (densely and sparsely granulated GH adenomas), mixed GH and prolactin cell adenomas, and monomorphous adenomas with primitive cells able to secrete GH and prolactin including the acidophilic stem cell adenoma and the mammosomatotroph cell adenoma. In this article, the author reviews the main pathological features of the GH-secreting adenomas and some of the molecular genetics mechanisms involved in their pathogenesis.