Breast cancer is the leading cause of cancer death in women worldwide. Insensitivity of tumor cells to drug therapies is an essential reason arousing such high mortality. Epithelial-mesenchymal transition (EMT) is deﬁned by the loss of epithelial characteristics and the acquisition of a mesenchymal phenotype. It is well known that EMT plays an important role in breast cancer progression. Recently, mounting evidence has demonstrated involvement of EMT in antagonizing chemotherapy in breast cancer. Here, we discuss the biological signiﬁcance and clinical implications of these ﬁndings, with an emphasis on novel approaches that effectively target EMT to increase the efﬁcacy of anticancer therapies.