Endothelial dysfunction is a key factor in the development and progression of heart failure (HF), with a bidirectional relationship between endothelial dysfunction and HF. The endothelium, a layer of cells lining blood vessels, regulates vascular tone, inflammation, and hemostasis. Endothelial dysfunction is characterized by a pro-inflammatory and pro-thrombotic state, which can be exacerbated by neurohormonal activation and shear stress in heart failure with reduced ejection fraction (HFrEF). It also contributes to endothelial damage in heart failure with preserved ejection fraction (HFpEF) due to systemic inflammation. Clinical trials suggest that drugs targeting endothelial dysfunction may be therapeutic options for HF and cardiovascular disease. The review highlights the pathogenetic correlation between endothelial dysfunction and HF, along with potential therapeutic strategies. Various methods, including intracoronary acetylcholine infusion, flow-mediated vasodilation (FMD), and peripheral arterial tonometry (PAT), are used to assess endothelial function. Endothelial dysfunction is associated with oxidative stress, inflammation, and impaired nitric oxide (NO) production, leading to vascular stiffness and impaired cardiac function. In HF, endothelial dysfunction contributes to vascular remodeling, increased oxidative stress, and adverse outcomes. Treatments such as ACE inhibitors, beta-blockers, and SGLT2 inhibitors may improve endothelial function and reduce cardiovascular events. Clinical trials are ongoing to evaluate the efficacy of targeting endothelial dysfunction in HF and cardiovascular disease. The review concludes that endothelial dysfunction is an emerging cardiovascular risk factor, and targeting it may offer new therapeutic options for HF and cardiovascular disease.Endothelial dysfunction is a key factor in the development and progression of heart failure (HF), with a bidirectional relationship between endothelial dysfunction and HF. The endothelium, a layer of cells lining blood vessels, regulates vascular tone, inflammation, and hemostasis. Endothelial dysfunction is characterized by a pro-inflammatory and pro-thrombotic state, which can be exacerbated by neurohormonal activation and shear stress in heart failure with reduced ejection fraction (HFrEF). It also contributes to endothelial damage in heart failure with preserved ejection fraction (HFpEF) due to systemic inflammation. Clinical trials suggest that drugs targeting endothelial dysfunction may be therapeutic options for HF and cardiovascular disease. The review highlights the pathogenetic correlation between endothelial dysfunction and HF, along with potential therapeutic strategies. Various methods, including intracoronary acetylcholine infusion, flow-mediated vasodilation (FMD), and peripheral arterial tonometry (PAT), are used to assess endothelial function. Endothelial dysfunction is associated with oxidative stress, inflammation, and impaired nitric oxide (NO) production, leading to vascular stiffness and impaired cardiac function. In HF, endothelial dysfunction contributes to vascular remodeling, increased oxidative stress, and adverse outcomes. Treatments such as ACE inhibitors, beta-blockers, and SGLT2 inhibitors may improve endothelial function and reduce cardiovascular events. Clinical trials are ongoing to evaluate the efficacy of targeting endothelial dysfunction in HF and cardiovascular disease. The review concludes that endothelial dysfunction is an emerging cardiovascular risk factor, and targeting it may offer new therapeutic options for HF and cardiovascular disease.