Endothelium regulates vascular homeostasis maintaining a healthy cardiovascular system but also plays a key role in tumor development, progression, and metastasis. Endothelial senescence can be driven by aging, DNA damage, oxidative stress, oncogenes and chemotherapy, and contributes to vascular dysfunction. Endothelial colony-forming cells (ECFC) are endothelial-committed progenitors with clonogenic potential, de novo angiogenic capacity and endothelial regenerative abilities. Studying ECFC senescence provides a novel approach to investigate the molecular mechanisms of endothelial dysfunction and response to treatment, in a noninvasive and personalized manner.