This review article, authored by Xia Wang and Ben He from the Department of Cardiology at Shanghai Chest Hospital, explores the molecular mechanisms and clinical implications of endothelial dysfunction in cardiovascular disease (CVD) and related complications. Endothelial dysfunction, characterized by reduced nitric oxide (NO) availability, oxidative stress, and inflammation, plays a crucial role in the initiation and progression of CVD. The article highlights recent research findings on the pathophysiological mechanisms involved, including the role of NO, oxidative stress, and inflammatory pathways. It also discusses the impact of endothelial dysfunction on various pathological conditions such as atherosclerosis, heart failure, diabetes, hypertension, chronic kidney disease, and neurodegenerative diseases. Additionally, the article reviews traditional and novel biomarkers of endothelial dysfunction and therapeutic strategies for endothelial protection and treatment of CVD and related complications. The review aims to improve understanding of emerging biomarkers and therapeutic approaches to reduce the risk of developing CVD and associated complications, as well as mitigate endothelial dysfunction.This review article, authored by Xia Wang and Ben He from the Department of Cardiology at Shanghai Chest Hospital, explores the molecular mechanisms and clinical implications of endothelial dysfunction in cardiovascular disease (CVD) and related complications. Endothelial dysfunction, characterized by reduced nitric oxide (NO) availability, oxidative stress, and inflammation, plays a crucial role in the initiation and progression of CVD. The article highlights recent research findings on the pathophysiological mechanisms involved, including the role of NO, oxidative stress, and inflammatory pathways. It also discusses the impact of endothelial dysfunction on various pathological conditions such as atherosclerosis, heart failure, diabetes, hypertension, chronic kidney disease, and neurodegenerative diseases. Additionally, the article reviews traditional and novel biomarkers of endothelial dysfunction and therapeutic strategies for endothelial protection and treatment of CVD and related complications. The review aims to improve understanding of emerging biomarkers and therapeutic approaches to reduce the risk of developing CVD and associated complications, as well as mitigate endothelial dysfunction.