<p>Chronic social stress is increasingly recognized as a significant contributor to endothelial dysfunction, a key precursor to various cardiovascular diseases. This review endeavors to explain the intricate molecular pathways underlying endothelial dysfunction triggered by chronic social stress and to explore its implications for treatment. We summarize the roles of neurotransmitters, neuromodulators, and immune factors in mediating stress-induced vascular changes. We examine recent advances in pharmacology aimed at targeting these pathways, presenting potential avenues for therapeutic intervention. Understanding these molecular mechanisms not only enhances our comprehension of stress-related vascular disorders but also offers the potential for developing targeted therapies to alleviate their adverse effects on cardiovascular health. This review underlines the importance of unraveling molecular pathways and highlights therapeutic opportunities for managing endothelial dysfunction resulting from chronic social stress.</p> Graphical Abstract <p>Chronic social stress has become a significant global issue, impacting various physiological systems and contributing to widespread endothelial dysfunction, a precursor to cardiovascular diseases. This review explores the intricate molecular pathways and discusses neurotransmitters, neuromodulators, and immune factors as mediators of stress-induced vascular changes. Recent pharmacological advancements targeting these pathways offer promising therapeutic interventions. Understanding these mechanisms enhances our comprehension of stress-related vascular disorders and enables the development of targeted therapies to mitigate adverse cardiovascular effects. This review emphasizes the importance of unraveling molecular pathways and highlights therapeutic opportunities for managing endothelial dysfunction resulting from chronic social stress.</p> <p></p>