Abstract: Endocrine therapies are effective to estrogen receptor α （ER） positive breast cancer. However， intrinsic and acquired endocrine resistance has always been the puzzle. ER is a nuclear protein， encoded by the ESR1 gene. ESR1 mutation plays an important role in endocrine resistance in ER positive breast cancer. ESR1-related genomic abnormalities include copy number changes，genomic rearrangements and missense point mutation. The finding of ER ligand binding domain（LBD） mutations can deepen the understanding of the endocrine resistance mechanisms. Furthermore，the dynamic changes between the agonist and antagonist conformation of the ER LBD mutants can also result in endocrine resistance. Now，studies on the target therapy of endocrine resistance mainly focus on increasing the doses of fulvestrant or tamoxifen or more potent selective estrin receptor modulators or estrogen receptor downregulators，new agents targeting ER co-activators，or targeting classical ER downstream genes （CDK4／6 inhibitors）. The studies on new agents are expected to resolve the endocrine resistance problems.