Mucositis is the result of the cytotoxic effects of many treatments given for hematological malignancies (HMs); it represents a major source of potentially devastating clinical complications and portrays negative consequences on the patient's management, such as a longer hospitalization, the need of analgesic and total parenteral nutrition use, and increased costs. The available measures for the prevention and treatment of mucositis have been substantially palliative, being limited to the control of pain, infection, bleeding and nutrition. However, in the last decade, a better insight into the complex pathogenesis of MBI has led to the development of novel therapeutic options, such as palifermin, which can provide tools potentially allowing a targeted approach to mucositis.