Growth regulation by estrogen in breast cancer 1 (GREB1) is one of the top estrogen (E2) responsive estrogen receptor (ER) target gene. GREB1 play pivotal role in the ER signaling dependent oncogenesis of breast cancers. GREB1 has been reported as a regulatory factor in ER signaling as it interact and regulate the function of ERα; the predominant subclass of ER. GREB1 acts as transcription coactivator that affects ER-chromatin interaction thereby modulate its downstream oncogenic signals that initiate the development and progression of breast cancer. Such intimate role of GREB1 places it as a therapeutic target and clinical biomarker for patient’s response to endocrine therapy. More recently Tamoxifen resistance in breast cancer was found to be regulated by the EZH2-ERα-GREB1 transcriptional axis. Despite the presence of such discrete evidence on the involvement of GREB1 in triggering the oncogenesis as well as drug response of breast cancer, there is very few compiled reports on the possible molecular mechanism how GREB1 could affect ER-associated tumor growth and subsequent therapeutic responses. Hence this review is written on the molecular roles of GREB1 in ER-positive breast cancer.