Oral mucositis is a common complication in cancer patients receiving chemotherapy and/or radiation therapy. Nearly all patients undergoing myeloablative therapy for stem-cell or bone marrow transplantation experience oral mucositis. Those receiving radiation therapy for head and neck cancer are at especially high risk. However,this toxicity also occurs with standard-dose chemotherapy and can be seen in association with treatment of many other tumor types. Oral mucositis significantly complicates cancer treatment by contributing to pain, dysphagia, weight loss, depression, higher risk of infection, decreased quality of life, and increased healthcare costs. This review summarizes the impact of oral mucositis in patients with cancer, including its pathogenesis, diagnosis, financial implications, and management. Current treatment guidelines are presented, and novel targeted therapies are discussed. Newer agents, such as palifermin (recombinant human keratinocyte growth factor-1), have been shown in clinical trials to reduce the incidence and severity of oral mucositis,and Saforis (an oral glutamine suspension) may also promote recovery from mucosal damage following chemotherapy or radiation therapy. Continued advances in understanding the pathobiology of oral mucositis should lead to the development of additional agents for its effective prevention and treatment in patients undergoing cancer therapy.