CDK4 and breast neoplasm: In those terms, along with this article, we have exemplified how the next-generation CDK inhibitors targeting CDK4/6 not only represent a beneficial alternative in ovarian and breast tumors—both in monotherapy or in combination with ETs or AIs—with several CTs presently supporting this choice (monarchE, MONALEESA, NATALEE, PALLET, among others), but we have also evaluated their potential as future players in the treatment of DIO.