Chronic treatment with renin-angiotensin system antagonists frequently causes deleterious hypotension during anesthesia. We present a case of marked intra-operative refractory hypotension in a 61-year-old male patient undergoing elective total thyroidectomy. He has been chronically treated for hypertension with angiotensin-converting enzyme inhibitors, angiotensin II receptor antagonists and atenolol, which were taken until the morning of surgery. After induction of anesthesia, marked hypotension which was refractory to fluid therapy occurred and did not respond to ephedrine administration. After continuous norepinephrine infusion, blood pressure increased and remained stable during the anesthesia period. Before extubation, norepinephrine was discontinued and recovery took place without complications. We discuss the anesthetic implication of chronic renin-angiotensin system antagonists treatment and intra-operative hemodynamic instability.