Prolongation of the QT interval associated with ventricular arrhythmias has been the most common cause of the restriction or withdrawal of drugs from the market in the past 10 years. Methadone, a synthetic opioid that is increasingly used for the management of chronic pain, has recently been implicated in the development of the prolonged QT syndrome. We present a case report of a patient who developed a prolonged QT while being treated with oral methadone for a chronic pain syndrome. Of particular interest in this patient is the fluctuation of the QT interval at a stable dose of methadone, suggesting that a single normal electrocardiogram (ECG) does not guarantee that the patient is not at risk of ventricular arrhythmias. After reviewing the current literature, we suggest that there is no dose of methadone that may be considered to be completely safe. Other risk factors for prolonged QT interval such as underlying cardiac abnormalities, electrolyte disturbances, and concurrent medications should be sought, and all patients should be monitored with serial ECGs even when methadone doses remain stable.