We anticipate that a better understanding of the mechanisms of intrinsic and acquired resistance to CDK4/6 inhibitors will lead to the development of improved therapeutic strategies that will ultimately benefit patients with prostate cancer, either by refining the role of the CDK4/6 inhibitors in this patient population or by informing the development of new cell cycle inhibitors and novel combination therapies with inhibitors of other interconnected pathways. Here, CDK4 is linked to prostate cancer.