Central neuromodulators (antidepressants, antipsychotics and other CNS targeted medications) are increasingly used for treatment of functional GI disorders (FGIDs), now recognized as disorders of gut-brain interaction. However, the available evidence and guidance for the use of central neuromodulators in these conditions is scanty and incomplete. In this Rome Foundation Working Team report, a multidisciplinary team summarized available research evidence and clinical experience to provide guidance and treatment recommendations.