Hormone receptor positivity and early stage diagnosis are generally considered signs of good prognosis in breast cancer. However, breast cancer all too frequently can become resistant to hormone-based therapies, and women can experience recurrence of their breast cancer decades after the diagnosis of early stage disease. To address the therapeutic needs for advanced and metastatic hormone receptor–positive (HR+) and human epidermal growth factor receptor 2–negative (HER2−) breast cancer, a number of new drugs have been tested and approved for this indication, including the class of drugs that works as cyclin-dependent kinase (CDK) 4/6 inhibitors. These drugs, often combined with other hormone-based therapy, have demonstrated considerable success in clinical trials and are now being used widely in oncology practices. Because all of the currently approved CDK4/6 inhibitor agents (palbociclib, ribociclib, and abemaciclib) are given orally, issues of patient comprehension of and adherence to prescribed regimens should be at the forefront of practitioners’ concerns about these drugs. In addition, ways to support and facilitate decision-making by patients related to this class of agents and other therapies recently approved for the same indication require focused attention by health-care providers. Oncology has continued to move toward a more patient-specific, precision medicine approach. Likewise, advanced practitioners have the opportunity to identify patient characteristics, preferences, and needs that are unique to individual patients to enhance precision treatment.