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Background: Very late effects of radiotherapy occur within decades after the initial exposure. Their development is induced by low doses of ionizing radiation (from 4 Gy per radiation series) and their clinical manifestations are difficult to distinguish from other independent diseases diagnosed in individuals not formerly treated with radiation. A long time period from the exposure confounds any causal relationships between radiation and adverse events. Still, these side effects not only reduce the patients quality of life but also lead to an early morbidity and mortality, hence generating significant costs in health care and social systems., Purpose: This article summarizes findings about the most common very late consequences of radiotherapy, which include cardiotoxicity, CNS toxicity, pneumotoxicity, renal toxicity and secondary malignancies. This issue is crucial in the group of children cancer patients, malignant lymphomas, testicular tumors and CNS tumors. Generally, the risk of very late effects of radiotherapy (RT) should be considered in all patients irradiated at a relatively early age with a high chance of long term survival. The risk of very late effects of RT is also one of the key limiting factors in the use of RT in the treatment of patients with benign lesions with longterm survival expectation, e. g. in patients with glomus tumors, neurofibromas, desmoid tumors or hemangiomas or other benign lesions (arterio venous malformations). Currently, the only known prevention of these very late adverse effects is to minimize the dose to critical structures to the lowest achievable level.