The article reviews the recent progress and current practices of CDK4/6 inhibitors in the treatment of breast cancer, particularly in hormone receptor-positive (HR+) and HER2-negative (HER2-) advanced breast cancer. CDK4/6 inhibitors have emerged as a pivotal treatment modality when combined with endocrine therapy (ET), significantly extending progression-free survival (PFS) and overall survival (OS) in these patients. The FDA has approved several CDK4/6 inhibitors, including Palbociclib, Abemaciclib, Ribociclib, and Dalpiciclib, for HR+/HER2- advanced breast cancer. These drugs are effective in both endocrine-sensitive and endocrine-resistant populations, with different regimens tailored to each group. For endocrine-sensitive patients, combinations with aromatase inhibitors (AIs) or fulvestrant have shown superior PFS and OS compared to AI monotherapy alone. In endocrine-resistant patients, fulvestrant plus CDK4/6i remains the preferred option, while abemaciclib is the preferred choice for primary endocrine resistance. CDK4/6i also demonstrate promise in patients with bone metastases and visceral metastases, improving PFS and OS. Additionally, preclinical and clinical studies suggest that CDK4/6i can enhance the response to HER2-targeted therapy and immunotherapy, although initial results from clinical trials combining CDK4/6i with immune checkpoint inhibitors have not shown significant benefits. The mechanism of action of CDK4/6 inhibitors involves blocking the phosphorylation of the retinoblastoma protein (Rb), which arrests the cell cycle in the G1 phase, thereby inhibiting tumor cell proliferation. However, these drugs can cause various toxicities, including neutropenia, liver enzyme elevations, and QT interval prolongation, which require careful monitoring and management. Overall, CDK4/6 inhibitors represent a significant advancement in the treatment landscape for HR+/HER2- advanced breast cancer, offering more tailored and effective treatment options.The article reviews the recent progress and current practices of CDK4/6 inhibitors in the treatment of breast cancer, particularly in hormone receptor-positive (HR+) and HER2-negative (HER2-) advanced breast cancer. CDK4/6 inhibitors have emerged as a pivotal treatment modality when combined with endocrine therapy (ET), significantly extending progression-free survival (PFS) and overall survival (OS) in these patients. The FDA has approved several CDK4/6 inhibitors, including Palbociclib, Abemaciclib, Ribociclib, and Dalpiciclib, for HR+/HER2- advanced breast cancer. These drugs are effective in both endocrine-sensitive and endocrine-resistant populations, with different regimens tailored to each group. For endocrine-sensitive patients, combinations with aromatase inhibitors (AIs) or fulvestrant have shown superior PFS and OS compared to AI monotherapy alone. In endocrine-resistant patients, fulvestrant plus CDK4/6i remains the preferred option, while abemaciclib is the preferred choice for primary endocrine resistance. CDK4/6i also demonstrate promise in patients with bone metastases and visceral metastases, improving PFS and OS. Additionally, preclinical and clinical studies suggest that CDK4/6i can enhance the response to HER2-targeted therapy and immunotherapy, although initial results from clinical trials combining CDK4/6i with immune checkpoint inhibitors have not shown significant benefits. The mechanism of action of CDK4/6 inhibitors involves blocking the phosphorylation of the retinoblastoma protein (Rb), which arrests the cell cycle in the G1 phase, thereby inhibiting tumor cell proliferation. However, these drugs can cause various toxicities, including neutropenia, liver enzyme elevations, and QT interval prolongation, which require careful monitoring and management. Overall, CDK4/6 inhibitors represent a significant advancement in the treatment landscape for HR+/HER2- advanced breast cancer, offering more tailored and effective treatment options.