Beta-blockers and calcium channel blockers result in a disproportionate number of fatalities from cardiac medication overdoses, and share similar characteristics. High-dose insulin is a superior therapy for both overdoses, but is likely synergistic with vasopressors; therefore we recommend starting vasopressors and high-dose insulin simultaneously. Digoxin remains an important cardiac poison and can likely be safely treated with smaller doses of fab fragments than in the past, except for patients in extremis. Extracorporeal membrane oxygenation is an invasive but promising nonspecific therapy for refractory shock from cardiotoxic overdose and should be considered primarily in cases of refractory cardiogenic shock.