More than half of cancers are treated with radiation therapy alone or in combination with surgery and/or chemotherapy. The goal of radiation therapy is to deliver enough ionising radiation to destroy cancer cells, without exceeding the level that the surrounding healthy cells can tolerate. Unfortunately, radiation-induced normal tissue injury is still a dose limiting factor in the treatment of cancer with radiotherapy. Early and late side-effects not only limit radiation dose escalation, but might also affect the patient's quality of life. Vascular injury is one of the most common effects of radiotherapy on normal tissues. Radiation-induced fibrogenesis is characterized by an orchestrated pathological wound-healing response in which the radiation-induced endothelium dysfunction plays a critical role. Irradiated endothelial cells acquire a proinflammatory, procoagulant and prothrombotic phenotype. The knowledge of molecular mechanisms involved in endothelium dysfunction following radiation is needed to identify therapeutic targets and develop strategies to prevent and /or reduce side-effects of radiation therapy.