Oral mucositis (OM) is an extremely debilitating side effect of certain high-dose chemotherapy and radiotherapy regimens. It is especially prevalent in patients with haematological malignancies who undergo myeloablative therapy and autologous haematopoietic stem cell transplantation (HSCT). Severe erosion of the lining of the oral cavity can make patients' everyday activities, including eating, drinking, swallowing, and talking, difficult or even impossible. Palifermin (Kepivance) was approved in Europe in 2005 for both prevention and treatment of this painful condition. It works at the epithelial level to help protect cells in the mouth and throat from the damage caused by chemotherapy and radiation, and to stimulate growth and development of new epithelial cells to build up the mucosal barrier. In the pivotal clinical trial, palifermin reduced the incidence, severity, and duration of severe OM. Palifermin was also well-tolerated; common adverse reactions reported included rash, pruritus, erythema, edema, pain, fever, arthralgia, mouth or tongue disorders, and taste alteration. In this article, nurses who are skilled in caring for patients undergoing HSCT review their clinical experience with palifermin, sharing practical advice about its reconstitution, dosing, and administration. By familiarising themselves with the use of palifermin, nurses can influence a shift in clinical practice away from OM symptom management to the more satisfactory situation of protecting patients against severe OM.