Despite advances in the diagnosis and management of acute coronary syndrome (ACS), atrial fibrillation (AF) remains a commonly encountered complication leading to adverse short- and long-term outcomes across the whole spectrum of ACS. At present, the underlying mechanisms of AF in myocardial ischemia remain incompletely understood. This article evaluates the incidence and trends of new-onset AF in ACS, its impact on ACS management and the associated prognostic significance in patients with acute ischemic heart disease. The safety and use of oral anticoagulation treatment in ACS patients on multiple antiplatelet agents are also explored. Further experimental and clinical studies are needed to improve current understanding and management of new-onset AF in ACS patients.