Platelet refractoriness is defined as the failure of platelets to show adequate increment after platelet transfusion. Platelets are important to the normal clotting and hemostasis process in the prevention of bleeding. Platelet refractoriness is a significant clinical concern because of resulting hemorrhagic emergencies, increased length of hospital stays, higher inpatient costs, and decreased survival. As part of the healthcare team, oncology nurses play a crucial role in early detection and using evidence-based management strategies for platelet refractoriness to limit the potential for associated morbidity and mortality.