While there has been a decline in the use of digoxin in patients with heart failure and atrial fibrillation, acute and chronic digoxin toxicity remains a significant clinical problem. Digoxin's narrow therapeutic window and nonspecific signs and symptoms of toxicity create clinical challenges and uncertainty around the diagnostic criteria of toxicity and responsive treatment choices for the bedside clinician. A systematic review of published literature on digoxin toxicity (34,587 publications over 6 decades, with 114 meeting inclusion criteria) was performed to develop 33 consensus statements on diagnostic and therapeutic approaches which were then evaluated through a modified Delphi process involving a panel of experts in cardiology, nursing, emergency medicine, and medical toxicology. The results demonstrate agreement about the need to consider time of ingestion and nature of the exposure (ie, acute, acute-on-chronic, chronic) and the use of digoxin immune Fab for life-threatening exposure to decrease risk of death. While several areas of continued uncertainty were identified, this work offers formalized guidance that may help providers better manage this persistent clinical challenge.