© 2022 University of Ankara. All rights reserved.Objective: The cancer is one of the serious health problems with high lethality in our country and also in the world. Breast cancer, the second most common type of cancer, is the most common of death in woman. Many innovative approaches have been discovered in drug treatments by elucidating the mechanisms of cancer cell formation. One of the innovative approaches is inhibition of cyclin-dependent kinase 4/6. In this review, general information about cyclin-dependent kinase 4/6 is given and the advantages and disadvantages of its inhibitors are emphasized. Result and Discussion: The development of resistance to endocrine therapies is a factor limiting the treatment process in estrogen receptor positive and human epidermal growth factor receptor 2 negative breast cancers. Cyclin-dependent kinase 4/6 inhibition pathway was discovered in retinoblastoma protein-positive breast cancers by targeting to overcome the endocrine resistance and arrest the cancerous cell at the mitosis checkpoint. Promising results in cancer therapy have been obtained with the combination of cyclin-dependent kinase 4/6 inhibitors with endocrine therapy.