In parallel with the continuous rise of cancer incidence, efficient treatment becomes an increasingly important public health concern. Radiotherapy has remained one of the most important anticancer approaches for clinical management of a variety of human tumors, as at least half of all oncological patients receive this therapy at some stages of their disease. With the hope to attain greater anticancer response, the interest in using natural plant-derived products as complementary treatments to conventional radiotherapy has substantially increased in the recent years. However, the interactions between phytochemicals and ionizing radiation are not always known and can be often unpredictable. Therefore, in this book, the current findings about the combined treatments of malignant cells with radiation and flavonoids, the largest group of human dietary plant polyphenols, are described. These data show that under carefully chosen dosage-schedule regimens, certain flavonoids or their natural mixtures can behave as potent radiosensitizers, augmenting radiotherapeutic efficacy in different preclinical cancer models. Such radiosensitizing action of flavonoids can be achieved through modulation of the redox status and suppression of several cellular survival pathways activated by radiotherapy, ultimately leading to the death of malignant cells. As flavonoids can concurrently protect normal healthy cells from irradiation-induced injury and thereby minimize toxic adverse reactions, use of these plant-derived agents as complementary approach to radiotherapy might open new avenues for enhancement of clinical outcome. Therefore, combining conventional anticancer modalities with conscious intake of flavonoid supplements as adjuvant agents might be an important future strategy to boost the therapeutic success in the treatment of various human malignancies.