Cortisol, widely recognized as the principal stress hormone, exerts extensive influence over numerous physiological processes throughout the body. This hormone functions as the primary glucocorticoid synthesized and released by the zona fasciculata of the adrenal cortex. The hypothalamic-pituitary-adrenal (HPA) axis governs cortisol production and secretion, and disruption of this regulatory system results in cortisol excess disorders such as Cushing syndrome or deficiency states such as Addison disease (see Image. Hypothalamic-Pituitary-Adrenal Axis). Cortisol influences metabolism, immune activity, cardiovascular tone, and the stress response by modulating glucose availability, protein catabolism, lipolysis, and inflammatory signaling. Excessive cortisol exposure, such as in Cushing syndrome, produces central obesity, muscle wasting, hypertension, and glucose intolerance. Cortisol deficiency, such as in Addison disease, causes fatigue, hypotension, weight loss, and hyperpigmentation. Understanding cortisol physiology enables clinicians to recognize deviations from normal regulation, interpret diagnostic findings accurately, and design targeted therapeutic strategies for endocrine and systemic disorders involving the HPA axis.