Radiation therapy is one of the three major treatment modalities used in eradicating malignant tumours. When ionising radiation is used to treat abdominal tumours, severe side effects largely due to mucosal damage in the alimentary tract are common, particularly when it is combined with chemotherapy. Radiation-induced mucositis may not only limit the therapeutic doses of combined treatment but also adversely affect the quality of life of the patient. Treatment strategies to treat and prevent radiation-induced mucositis have been reviewed and published in the Clinical Practice Guidelines, 2004. However evidence supporting an effective treatment approach is tenuous, probably because the mechanistic evolution of radiation-induced mucositis is poorly understood. Several animal models have been used to examine the various effects of radiation but no single animal model has been able to effectively capture the effects of radiation on the alimentary tract at the molecular level before symptoms begin. This review will outline the events which occur following radiation exposure; from chromosomal aberrations in the mucosal cells leading to apoptotic and mitotic death, to the evolution of mucositis involving changes in gene activations and signaling. A better understanding of the mechanisms of radiation therapy-induced mucositis is necessary as it will allow for future pharmaceutical interventions to alleviate if not eliminate the debilitating side effects.