Cardiac and central nervous system (CNS) safety of opioid agonist therapy is increasingly scrutinized given rising opioid-related fatalities. Knowledge gaps exist regarding the risk of cardiac toxicity of drugs beyond methadone and buprenorphine. A number of over the counter preparations appear to have a QTc-prolongation liability. Numerous drug-drug interactions may increase this liability. These will be presented in categories for practical implementation. We will also discuss the implementation of a collaborative training of psychiatrists that include ECG interpretation with oversight by cardiologists. This training proved to be preliminarily successful. These activities are supported by ongoing quality and accreditation processes in Opioid Treatment Programs.