This review article encapsulates targeted therapies (including CDK4/6 inhibitors, PI3K inhibitors, PARP inhibitors, and Proteolysis-targeting chimeras) and endocrine therapies (such as Aromatase Inhibitors, Selective estrogen receptor modulators, Selective Estrogen Receptor Degraders, Complete estrogen receptor antagonists) employed in the treatment of HR+/HER2– breast cancer. The gene discussed is ESR1; the disease is breast cancer.