Abstract: Cellular proliferation， growth， and division are tightly controlled by the cell-cycle regulatory machinery. Recently， cyclin-dependent kinase 4 and 6（CDK4/6） inhibitors were identified to be useful in breast cancer patients with positive estrogen receptor or amplified HER-2， whereas the role remains controversial in triple-negative breast cancer. It is of great importance to investigate the predictive biomarkers for identifying which subgroup of breast cancer patients would mostly benefit from such treatment. Moreover， tumor suppressor retinoblastoma（Rb） plays a pivotal importance in breast cancer， and cyclin D-CDK4/6-Rb pathway， governing the cell cycle restriction point in breast cancer， is a potential target for anticancer therapy. In this article, we review the preclinical and clinical data and describe the future development on the role of CDK4/6 inhibitors in breast cancer.