Over recent decades, the prevalence of aortic valve stenosis (AVS) has been constantly increasing possibly owing to the aging of general population. Severe AVS as determined by an aortic valve area (AVA) of <1 cm2 has been regarded as a serious clinical condition potentially associated with a variety of adverse outcomes, including sudden cardiac death (SCD). However, patients with severe AVS (in the absence of overt high-risk features) are usually evaluated and managed exclusively based on symptomatology or imperfect prognostic tools including exercise testing and biomarkers, with a potential risk of mismanagement, suggesting the need for further objective risk stratifiers in this setting. Within this context, copeptin (C-terminal pro-vasopressin), a novel neurohormone widely considered as the surrogate marker of the arginine-vasopressin (AVP) system, may potentially serve as a reliable prognostic and therapeutic guide (e.g. timing of aortic valvular intervention) in patients with severe AVS largely based on its hemodynamic, fibrogenic as well as autonomic implications in these patients. Accordingly, the present paper aims to discuss clinical and pathophysiological implications of copeptin in the setting of AVS along with a summary of biomarkers and other prognostic tools used in this setting.