Recent trial data have expanded the horizons of newer indications of non-vitamin K oral anticoagulants (NOAC). Most recently they are being evaluated for use in embolic stroke of undetermined source (ESUS). ESUS are particularly known for their recurrences. So, identifying the causes and treating those etiological factors are the keys to secondary prevention of ESUS. Although traditional experts still opine for the use of antiplatelets for secondary prevention of ESUS as for other causes of embolic stroke, there are still room for improvement in delivery of optimal treatment strategy. So, NOAC is being tried as an alternative to traditional atiplatelet therapy in head-to-head trials. Unfortunately, recent trial data (from NAVIGATE-ESUS and RESPECT-ESUS) have not shown any added benefits (with comparable bleeding risk) of NOAC compared to aspirin in prevention of ESUS. This review intends to highlight the concept of ESUS, its varied etiologies, discuss the published and ongoing trials and tries to dig the reasons why the overall trial data have been disappointing. It also discusses the arenas where NOAC may be proved to be better than antiplatelets. Overall, we have stressed on the personalized case-to-case basis decision making while choosing the appropriate therapy in secondary prevention of ESUS.