For millions of women, breast cancer remains a potentially life-endangering 
diagnosis. With advances in research, new therapies targeted to tumor biology 
are emerging to treat the most common form of this disease. Cyclin-dependent 
kinase (CDK) 4/6 inhibitors are a new class of therapeutic agents that have the 
potential to improve the outcomes of patients with hormone receptor-positive 
(HR(+)) breast cancer. Three CDK 4/6 inhibitors have been investigated for the 
treatment of HR(+) breast cancer, including palbociclib (PD 0332991), ribociclib 
(LEE011), and abemaciclib (LY2835219). Palbociclib recently received accelerated 
Food and Drug Administration approval for the treatment of HR(+) metastatic 
breast cancer in combination with letrozole, and recent data suggest improved 
outcome when combined with fulvestrant. In this article, the mechanism of action 
of CDK 4/6 inhibitors, preclinical studies on their efficacy, ongoing clinical 
trials in breast cancer, and toxicity profiles are reviewed.