In the comprehensive treatment of breast cancer, endocrine therapy has become one of the effective methods for hormone receptorpositive (HR+) breast cancer. However, the effectiveness of endocrine therapy has been limited by primary resistance and acquired resistance as its long-term application. The clinical trials associated with cyclin-dependent protein kinases (CDKs) inhibitors have proven that the CDK4/6 inhibitors have an effect in reversing the resistance of endocrine therapy for the patients with HR+ and human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer, and have significance advantage in progression free survival. CDK4/6 inhibitors can regulate cell cycle mainly by the CDK4/6-cyclin D-retinoblastoma (RB) pathway, which is also a key downstream target of estrogen receptor (ER) signal. Therefore, inhibiting the activity of CDK4/6 can restore cell cycle control and further block tumor cell proliferation. This review describes the efficacy, safety and pharmacokinetics of three CDK4/6 inhibitors (palbociclib, ribociclib and abemaciclib) in clinical trials of HR+ and HER2- advanced breast cancer. This article also reviews the latest research results about CDK4/6 inhibitors stimulating the immune response and blocking the distant metastasis of triplenegative breast cancer cell lines.