Doxorubicin (DOX), or adriamycin, is an anthracycline antineoplastic drug widely used in the chemotherapy of a large variety of cancers due to its potency and action spectrum. However, its use is limited by the toxicity on healthy cells and its acute and chronic side effects. One of the developed strategies to attenuate DOX toxicity is the combined therapy with bioactive compounds such as flavonoids. This review embraces the role of flavonoids on DOX treatment side effects. Protective properties of some flavonoidss against DOX toxicity have been investigated and observed mainly in heart but also in liver, kidney, brain, testis or bone marrow. Protective mechanisms involve reduction of oxidative stress by decrease of ROS levels and/or increase antioxidant defenses and interferences with autophagy, apoptosis and inflammation. Studies in cancer cells have reported that the anticancer activity of DOX was not compromised by the flavonoids. Moreover, some of them increased DOX efficiency as anti-cancer drug even in multidrug resistant cells.