Over the last 20 years there were multiple initiatives of Regulatory Agencies, both in the U.S. (FDA) and in Europe (EMA), which created disconcert and alarm in the world of psychiatry. Most often these initiatives have involved interactions, considered potentially dangerous, between antipsychotics or antidepressants and cardiovascular risks. The latest were related to two drugs known to be effective antidepressants such as citalopram (by FDA) and its active enantiomer, escitalopram (only by the EMA), in connection with a possible lengthening of the QT interval. This critical review, which provides the joint opinion of a cardiologist and a psychiatrist both with specific expertise, aims to put into perspective the actions of regulatory agencies regarding the association between antidepressants, QT interval and cardiac arrhythmias; to review the physiological basis and mechanisms underlying this issue; to critically analyze the relevant evidences and the other cardiovascular effects of these drugs, and to draw reasonable conclusions for psychiatrists who treat depressed patients.