Adrenocorticotropic hormone (ACTH) is secreted by the anterior pituitary and stimulates cortisol secretion from the adrenal cortex via the hypothalamic-pituitary-adrenal (HPA) axis. ACTH is clinically important because it regulates cortisol production, a hormone with broad physiologic effects, including suppression of inflammation, stimulation of metabolic activity, and elevation of blood glucose, which are critical components of the stress response. Dysregulation of ACTH activity is associated with disorders such as Cushing syndrome and primary adrenal insufficiency. A thorough understanding of ACTH physiology is essential for accurate diagnosis and management of disorders affecting cortisol regulation. Insight into ACTH dynamics enables clinicians to identify underlying pathologies, tailor therapeutic strategies, and anticipate complications arising from dysregulated cortisol levels.