The orally bioavailable CDK4 and 6 inhibitors—abemaciclib, palbociclib, and ribociclib—have been established standard-of-care options in HR+/HER2- metastatic breast cancer for a while, and recently, abemaciclib was also approved in the adjuvant setting for the treatment of patients with early breast cancer (EBC) at high risk of early recurrence. This brings new hope to a group of patients with EBC who have been underserved by existing therapeutic options and have faced an unacceptably high risk of recurrence. With great progress in clinical research come questions about how to translate it into improvements in clinical practice. Which patients are/are not candidates for adjuvant CDK4 and 6 inhibition based on the recent FDA approval and updated ASCO recommendations? What is the role of Ki-67 testing in determining patient eligibility for treatment? How should risk be assessed to inform treatment selection and improve outcomes in patients with HR+/HER2- EBC? These questions and others are answered in this succinct educational activity to help make the most of this new adjuvant therapy option for the benefit of patients.