Resistance to chemotherapy treatment, which may lead to limited efficacy of systemic therapy in breast cancerpatients, is multifactorial. Among the mechanisms of resistance to chemotherapy treatment, there are those closelyrelated to estrogen receptor α, P-glycoprotein, multidrug resistance-related protein, glutathione S-transferasepi and topoisomerase-II. ERα is ligand-activated transcription factor that regulates gene expression and plays acritical role in endocrine signaling. In previous preclinical and clinical studies, positive ERα expression in breastcancer cells was correlated with decreased sensitivity to chemotherapy. This article reviews current knowledgeon the predictive value of ERα with regard to response to chemotherapy. Better understanding of its role mayfacilitate patient selection of therapeutic regimens and lead to optimal clinical outcomes.