Cardiac arrhythmias still represent a major health problem worldwide, at least in part because the fundamental pathogenic mechanisms are not fully understood, thus affecting the efficacy of therapeutic measures. In fact, whereas cardiac arrhythmias are in most cases due to structural heart diseases, the underlying cause remains elusive in a significant number of patients despite intensive investigations even including postmortem examination and molecular autopsy. A large body of data progressively accumulated during the last decade provides strong evidence that autoimmune mechanisms may be involved in a significant number of such unexplained or poorly explained cardiac arrhythmias.