Oropharyngeal mucositis is an acute and distressing toxic effect of chemotherapy and head and neck irradiation. This oral sequela significantly impairs the daily functioning and quality of life of patients. The biological basis of mucositis is quite complex, involving sequential interaction of chemotherapeutic drugs or irradiation on mitosis of proliferating epithelium, a number of cytokines, and elements of oral microbial environment. Various interventions based on biological attenuation have been tested for mucositis. Such interventions have been reviewed elsewhere; however, most reviews focus on biomedical outcomes. Little attention has been paid to mucositis outcomes with oral morbidity or psychosocial aspects. The purpose of this article is to review the current research studies on the prevention and treatment of oropharyngeal mucositis following chemotherapy, radiotherapy, and bone marrow transplantation with an emphasis on biomedical, oral symptomatic, and functional impairment outcomes. In addition, further avenues of mucositis management, including psychotherapeutic intervention and integrated and stage-based treatment approaches are discussed.