Li C, et al. - Given reversal of endocrine therapy (ET) resistance as well as improvement of prognosis of patients with hormone receptor-positive (HR+) advanced breast cancer is offered by cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors but progression eventually occurs, thus, researchers herein tried to summarize the recent therapeutic strategies for patients who have suffered progression after CDK4/6 inhibitors, on the basis of evidence from clinical trials and retrospective studies. They also address the potential options post CDK4/6 inhibitors. They analyzed phase I, II and III clinical trials and retrospective studies post CDK4/6 inhibitors. Current evidence lends support to the following inferences about treatment strategies post CDK4/6 inhibitor use: (1) clinical benefits [median progression-free survival (mPFS): 5.7 months] are conferred by CDK4/6 inhibitors plus exemestane and everolimus, (2) a different regimen (including an ET-based regimen) can replace CDK4/6 inhibitor regimens. Effectiveness of everolimus plus exemestane post CDK4/6 inhibitors (mPFS: 3.6 months; median overall survival: 15.6 months) is indicated by limited evidence. (3) Continuing ET is not necessarily required when CDK4/6 inhibitor resistance is developed, as chemotherapy can be initiated. Mammalian target of rapamycin inhibitors as well as PIK3 inhibitors behave as upstream signaling pathway of CDK4/6 inhibitors and are associated with the reasons for CDK4/6 inhibitor resistance. Therefore, CDK4/6 inhibitor resistance may be overcome by these drugs.