In 2014, the new concept of embolic stroke of undetermined source (ESUS) was first proposed by cryptogenic stroke/ESUS International Working Group. In the past 5 years, related clinical researches of ESUS have been deepened, and the results of many large clinical studies have been published. However, the guiding significance of this new concept to clinical practice is still controversial. By reviewing the background, diagnostic criteria, assessment, common emboli sources, anticoagulant therapy research advances and related limitations of ESUS, and analyzing the possible causes of negative anticoagulant therapy results, we explored the clinical value of this new classification.