Oral mucositis is a distressing toxic effect of systemic chemotherapy with many commonly utilized drugs and of head and neck irradiation in patients with cancer. The agents and methods that have been used and studied in chemotherapy- and radiotherapy-induced oral mucositis, their mechanisms of action, and the current knowledge of their efficiency to reduce the incidence, severity or shorten the duration of oral mucositis are reviewed in this article. Oral cooling is a cheap and available method to lower the severity of bolus 5-fluorouracil-induced oral mucositis. However, more effective methods are needed. Results of studies with granulocyte-macrophage colony-stimulating factor or granulocyte colony-stimulating factor are promising. Lasers are partly beneficial, but equipment-demanding. Modification of the chemotherapy regimen resulting in shortening of the exposition time to chemotherapy agents or chronomodulation of chemotherapy has been shown to lower mucosal toxicity of some regimens. Results of animal studies with locally applied transforming growth factor beta 3 and interleukin-11 are also promising. Based on the findings of the role of the inflammatory cascade in the response of normal tissues to chemotherapy and radiotherapy, anti-inflammatory drugs might be beneficial. At the present time, no agent has been shown to be uniformly efficacious and can be accepted as standard therapy of chemotherapy- and radiotherapy-induced oral mucositis. Further intensive research is needed.