Overdose by calcium channel blocker (CCB) antihypertensive agents has been shown to be a cause of significant morbidity and can often be fatal. (1) Although overdoses of calcium-channel blockers and beta blockers are uncommon, they have a high mortality rate, and management may be complicated. (2) Amlodipine, a dihydropyridine CCB, can cause prolonged hypotension in overdose. (3) We report a case of severe Amlodipine/Atenolol overdose that was refractory to multiple therapeutic approaches but rapidly responded to plasmapheresis. We describe the case of a previously healthy 25-year-old lady presented after ingesting 30 tablets of Amlodipine 5 mg/Atenolol 50 mg in a suicide attempt. The patient was initially managed with fluid resuscitation, calcium boluses, glucagon bolus, methylene blue boluses and multiple vasoactive agents. Hyperinsulinemic euglycemic therapy was initiated when hypotension persisted despite conventional treatments but was stopped later due to life threatening hypoglycemia and hypokalemia. Refractory hypotension prompted the use of plasmapheresis in an attempt to lower serum amlodipine levels as knowing that amlodipine is highly protein bound. Plasmapheresis is a procedure used to remove pathologic substances from a patient’s blood that has proven useful in some cases of drug overdose. (1) A dramatic improvement of cardiovascular stability was already observed during plasmapheresis. The primary outcomes were to reduce mortality and improve hemodynamic parameters. The secondary outcomes included reduce length of stay in intensive care unit, duration of vasopressor use and functional outcomes. (4) Conclusion: This case demonstrates that a Plasmapheresis can be effective in restoring hemodynamic stability in severe calcium channel blocker toxicity and recommend its use in patients with calcium channel blocker toxicity that is not responsive to traditional therapies.