This review is focused on the prevailing question of physiological and clinical consequences of chronic elevation of cortisol and ADH levels, concentrating on their individual and collective foe. Water retention and hyponatremia due to increased ADH, such as seen in syndrome of inappropriate antidiuretic hormone (SIADH) secretion, may lead to acute neurologic symptoms including seizures and coma1 or chronic complications like osteoporosis, cognitive impairment2 and gait impairment. Systemic disorders including hypertension, insulin resistance, visceral obesity, muscles atrophy and bone loss mood disorders and immune suppression, which have been associated with increased cortisol levels identified in endogenous Cushing's syndrome patients or in long-term GC therapy. The diagnostic challenge of differentiating SIADH from adrenal insufficiency and other electrolyte abnormalities, especially in patients who are ill or have undergone surgery, also is addressed by the study. Similarly, the interrelationship of cortisol and ADH regulation are described, stressing upon complex neuroendocrine feedback mechanisms. Decline of morbidity and improvement of the final outcome may be achieved by early diagnosis and correct therapy for these hormonal disorders.