Colchicine is commonly prescribed for treatment of inflammatory conditions but has a narrow therapeutic window and dangerous toxicity profile. Here we describe a case of survival after massive unintentional colchicine overdose treated with plasmapheresis and renal replacement therapy. A 37 year old male with history of pericarditis presented to the Emergency Department with a chief complaint of nausea, vomiting, and diarrhea after unintentionally ingesting 36 mg of colchicine 17 h prior to arrival. An initial colchicine concentration resulted at 5.1 ng/mL (30 h post-ingestion) and peaked at 12 ng/mL (40 h post-ingestion). He was treated with continuous kidney replacement therapy (CKRT) beginning on his first day of hospitalization and with plasmapheresis on hospital days two through four. The patient's course was complicated by multiorgan failure including coagulopathy, respiratory failure, neuropathy, renal failure, pancytopenia, and heart failure. He was discharged to inpatient rehabilitation on hospital day 24. On clinical follow up four months after discharge the patient was found to have no significant persistent morbidity related to colchicine overdose.