Empty follicle syndrome (EFS), defined by the failure to retrieve oocytes despite normal follicle development following controlled ovarian stimulation, is a multifactorial condition in assisted reproductive treatment and categorized into genuine EFS (GEFS) and false EFS (FEFS). The etiology of GEFS is complex, involving genetic factors and ovarian dysfunction, with mutations in LHCGR and ZP genes being the major causes. However, the underlying cause remains unknown in most patients. Targeted therapies based on specific etiologies are crucial in GEFS management. Oocyte donation is considered as a final viable option when other precision treatments prove ineffective. The etiology of FEFS is relatively clear, primarily associated with inappropriate administration of ovulation-triggering drugs, which can be rescued by a second injection of human chorionic gonadotropin or change the medication regimen. This review summaries current advances in the diagnosis and treatment of EFS, aiming to provide guidance for clinical management and further etiology research.