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Digoxin, a cardiac glycoside, is commonly prescribed for the management of congestive heart failure, atrial fibrillation or flutter, and certain cardiac arrhythmias. However, its clinical use is limited by its narrow therapeutic index, which predisposes patients to toxicity. At elevated concentrations, digoxin toxicity can present with gastrointestinal disturbances, visual changes, and cardiac arrhythmias. This systematic review aims to summarize reported cases of digoxin toxicity, focusing on associated risk factors, drug-drug interactions, and clinical manifestations. A comprehensive literature search was conducted using PubMed and Ovid MEDLINE with the keywords “digoxin” and “toxicity.” Clinical and laboratory features of toxicity were extracted and analyzed. Of the 2,399 articles identified, only 10 met the inclusion criteria for final review. In 4 of the 10 cases, diuretics were implicated as interacting medications. Commonly reported symptoms included nausea, vomiting, visual disturbances, bradycardia, and elevated serum digoxin levels. Identified risk factors for toxicity included female sex, advanced age (60–91 years), renal impairment, and concomitant drug use. Notably, toxicity was observed even at therapeutic or low serum digoxin concentrations in the presence of these risk factors. The most frequent clinical manifestations were gastrointestinal symptoms, vision changes, and bradycardia.