Atrial fibrillation (AF) is associated with thrombus formation in the left atrial appendage and systemic embolic events including ischemic stroke. Cardiogenic thromboembolism can also occur in the absence of clinical AF as a result of various pathological conditions affecting the endocardium. The inconsistent temporal relation between AF and ischemic events has stimulated exploration for factors other than clinical AF that contribute to thromboembolism. These include subclinical AF, a thrombogenic atrial cardiomyopathy, and left atrial appendage dysfunction and embolism from other sources. In conclusion, thromboembolism during normal sinus rhythm is likely multifactorial, involving intertwined pathologic processes. Patients at risk, if accurately identified, could theoretically benefit from anticoagulation.