Endothelial senescence is a critical factor in vascular aging and contributes to various age-related diseases. Endothelial cells, which line blood vessels, undergo senescence characterized by reduced regeneration, inflammation, and altered secretory profiles. This process is more pronounced in microvascular endothelial cells, leading to decreased capillary density, impaired blood flow, and tissue hypoperfusion. Senescent endothelial cells contribute to age-related diseases by secreting pro-inflammatory factors and disrupting tissue homeostasis. Senolytic drugs, which target senescent cells, show promise in delaying aging and treating age-related conditions. However, the heterogeneity of endothelial senescence across different vascular beds and tissues presents challenges in developing targeted therapies. Senescent cells in the brain and heart are particularly implicated in neurodegenerative and cardiovascular diseases. Targeting endothelial senescence through senolytic strategies, such as drugs like dasatinib and quercetin, or lifestyle interventions like aerobic exercise, may offer therapeutic benefits. Despite progress, challenges remain in safely and effectively eliminating senescent cells without adverse effects. Further research is needed to develop precise and context-specific therapies for endothelial senescence.Endothelial senescence is a critical factor in vascular aging and contributes to various age-related diseases. Endothelial cells, which line blood vessels, undergo senescence characterized by reduced regeneration, inflammation, and altered secretory profiles. This process is more pronounced in microvascular endothelial cells, leading to decreased capillary density, impaired blood flow, and tissue hypoperfusion. Senescent endothelial cells contribute to age-related diseases by secreting pro-inflammatory factors and disrupting tissue homeostasis. Senolytic drugs, which target senescent cells, show promise in delaying aging and treating age-related conditions. However, the heterogeneity of endothelial senescence across different vascular beds and tissues presents challenges in developing targeted therapies. Senescent cells in the brain and heart are particularly implicated in neurodegenerative and cardiovascular diseases. Targeting endothelial senescence through senolytic strategies, such as drugs like dasatinib and quercetin, or lifestyle interventions like aerobic exercise, may offer therapeutic benefits. Despite progress, challenges remain in safely and effectively eliminating senescent cells without adverse effects. Further research is needed to develop precise and context-specific therapies for endothelial senescence.