This review summarizes the pharmacodynamics and adverse effects of doxorubicin, an anthracycline chemotherapy drug used in the treatment of various cancers. The study highlights the complex mechanisms by which doxorubicin exerts its anticancer effects and causes cardiotoxicity. Doxorubicin acts through two main pathways: intercalation into DNA and disruption of topoisomerase-II-mediated DNA repair, and generation of reactive oxygen species (ROS) that damage cellular membranes, DNA, and proteins. Additionally, doxorubicin can enter the nucleus and poison topoisomerase-II, leading to DNA damage and cell death. Cardiotoxicity is a major limitation of doxorubicin therapy, with the total cumulative dose being the primary factor in predicting toxicity. Two main theories explain the mechanism of doxorubicin-induced cardiotoxicity: iron-related free radicals and the formation of doxorubicinol metabolite, and mitochondrial disruption. The iron chelator dexrazoxane is protective against doxorubicin-induced toxicity, but other iron chelators like deferasirox do not provide the same protection, suggesting an alternative mechanism involving interaction with topoisomerase-II. The study also discusses mechanisms of drug resistance, including the role of transporters such as ABCB1 and ABCC1, and the amplification of topoisomerase-II. Pharmacogenomic studies have identified genetic variants associated with doxorubicin-induced cardiotoxicity, including those in the NAD(P)H oxidase complex and doxorubicin transporters. These variants may influence the risk of cardiotoxicity and response to treatment. The review emphasizes the importance of pharmacogenomics in understanding individual variability in doxorubicin response and toxicity. It highlights the need for further research to identify genetic markers that can help predict treatment outcomes and reduce toxicity. The study also discusses drug-drug interactions, such as those with trastuzumab and taxanes, which can increase cardiotoxicity. Overall, the review underscores the complexity of doxorubicin's mechanisms and the potential of pharmacogenomics to improve its clinical use.This review summarizes the pharmacodynamics and adverse effects of doxorubicin, an anthracycline chemotherapy drug used in the treatment of various cancers. The study highlights the complex mechanisms by which doxorubicin exerts its anticancer effects and causes cardiotoxicity. Doxorubicin acts through two main pathways: intercalation into DNA and disruption of topoisomerase-II-mediated DNA repair, and generation of reactive oxygen species (ROS) that damage cellular membranes, DNA, and proteins. Additionally, doxorubicin can enter the nucleus and poison topoisomerase-II, leading to DNA damage and cell death. Cardiotoxicity is a major limitation of doxorubicin therapy, with the total cumulative dose being the primary factor in predicting toxicity. Two main theories explain the mechanism of doxorubicin-induced cardiotoxicity: iron-related free radicals and the formation of doxorubicinol metabolite, and mitochondrial disruption. The iron chelator dexrazoxane is protective against doxorubicin-induced toxicity, but other iron chelators like deferasirox do not provide the same protection, suggesting an alternative mechanism involving interaction with topoisomerase-II. The study also discusses mechanisms of drug resistance, including the role of transporters such as ABCB1 and ABCC1, and the amplification of topoisomerase-II. Pharmacogenomic studies have identified genetic variants associated with doxorubicin-induced cardiotoxicity, including those in the NAD(P)H oxidase complex and doxorubicin transporters. These variants may influence the risk of cardiotoxicity and response to treatment. The review emphasizes the importance of pharmacogenomics in understanding individual variability in doxorubicin response and toxicity. It highlights the need for further research to identify genetic markers that can help predict treatment outcomes and reduce toxicity. The study also discusses drug-drug interactions, such as those with trastuzumab and taxanes, which can increase cardiotoxicity. Overall, the review underscores the complexity of doxorubicin's mechanisms and the potential of pharmacogenomics to improve its clinical use.