Selective estrogen receptor modulators (SERMs) are synthetic molecules which bind to estrogen receptors (ER) and can modulate their transcriptional capabilities in different ways in diverse estrogen target tissues. Unfortunately, the use of resistant therapy is associated with acquired resistance. Several molecular mechanisms have been proposed to be responsible for endocrine resistance in breast cancer, including MIR-451, FGF and FGFR, ADAM12, fibronectin and other soluble stromal factors, PELP1-KDM1, HER2, NOTCH, delta Ef1, mTOR, AKT/mTOR, Pi3K/AKT, Pi3K/AKT/mTOR, NF kappa B, LMTK3, IGF1R, cyclin E2, IRF1, Tab2, and SRC-1. Further research is needed to know more about endocrine resistance.