Amiodarone is used worldwide to treat cardiac arrhythmias, as well as highly symptomatic cases of atrial fibrillation. With this expanded use, especially following its 1985 United States Food and Drug Administration approval, and its use as a long-term therapy in common practice, reports of cancers temporarily related to amiodarone have begun to increase. Animal studies, several clinical trials, numerous case reports, and a population-based cohort study have suggested that cancers may be associated with amiodarone use. This review focuses on the ever increasing evidence in the literature that suggests amiodarone therapy, especially with long-term use, may increase the potential risk of cancer development. It also expresses the need for more definitive studies to be conducted to provide clinicians with a clear answer to this important question.