This article provides a comprehensive overview of the pharmacodynamics and adverse effects of doxorubicin, an anthracycline drug widely used in cancer treatment. The study highlights the mechanisms by which doxorubicin acts in cancer cells, including DNA intercalation and disruption of topoisomerase-II-mediated DNA repair, as well as the generation of free radicals that damage cellular membranes, DNA, and proteins. The mechanisms of cardiotoxicity are also discussed, focusing on iron-related free radicals and mitochondrial disruption. The article reviews the genetic variations associated with doxorubicin response and toxicity, particularly in the context of pharmacogenomics (PGx). Key variants in genes such as ABCC1, ABCC2, CAT, CBR3, CYBA, NCF4, and RAC2 are linked to cardiotoxicity. The impact of these variants on clinical outcomes, such as cardiotoxicity and survival, is summarized. The article also addresses resistance mechanisms, including those involving ABCB1, ABCC1, and other transporters, and TOP2A amplification. Finally, the authors emphasize the need for large-scale studies to better understand the complex interactions between doxorubicin and other treatments, as well as the role of PGx in predicting individual responses and toxicity.This article provides a comprehensive overview of the pharmacodynamics and adverse effects of doxorubicin, an anthracycline drug widely used in cancer treatment. The study highlights the mechanisms by which doxorubicin acts in cancer cells, including DNA intercalation and disruption of topoisomerase-II-mediated DNA repair, as well as the generation of free radicals that damage cellular membranes, DNA, and proteins. The mechanisms of cardiotoxicity are also discussed, focusing on iron-related free radicals and mitochondrial disruption. The article reviews the genetic variations associated with doxorubicin response and toxicity, particularly in the context of pharmacogenomics (PGx). Key variants in genes such as ABCC1, ABCC2, CAT, CBR3, CYBA, NCF4, and RAC2 are linked to cardiotoxicity. The impact of these variants on clinical outcomes, such as cardiotoxicity and survival, is summarized. The article also addresses resistance mechanisms, including those involving ABCB1, ABCC1, and other transporters, and TOP2A amplification. Finally, the authors emphasize the need for large-scale studies to better understand the complex interactions between doxorubicin and other treatments, as well as the role of PGx in predicting individual responses and toxicity.