Acromegaly is an endocrine disorder characterized by dysregulated hypersecretion of growth hormone (GH), leading to an overproduction of insulin-like growth factor 1 (IGF-1). The etiology is usually a GH-secreting pituitary adenoma with the resultant presentation of coarse facial features, frontal bossing, arthritis, prognathism (protrusion of the mandible), and impaired glucose tolerance, among others. Most pituitary adenomas arise due to sporadic mutations that lead to unregulated cellular division, subsequent tumor formation, and resultant GH hypersecretion. Major scientific organizations and authorities in endocrinology release regularly updated guidelines for diagnosing and managing acromegaly. We have holistically evaluated four data-driven and evidentiary approaches in the management of acromegaly to compare and contrast these guidelines and show their salient differences. These guidelines have been reviewed because they are major authorities in acromegaly management. In this comprehensive article, differences in the diagnosis and treatment recommendations of the discussed guidelines have been highlighted. Our findings showed that diagnosing modalities were similar among the four approaches; however, some guidelines were more specific about additional supporting investigations to confirm a diagnosis of acromegaly. For management options, each guideline had suggestions about ideal therapeutic outcomes. Treatment options were identical but salient differences were noticed, such as the addition of combination therapy and alternative therapy in the setting of failure to respond to first and second-line treatments. Reviewing clinical guidelines for various pathologies encourages sharing ideas among medical practitioners and ensures that global best practices are adopted. Therefore, a constant review of these clinical practice guidelines is necessary to keep clinicians up to date with the latest trends in patient management.