Fatigue is a common complaint of individuals receiving treatment for cancer. There is a dearth of rigorous research investigating the clinical course and prognosis of fatigue over the course of radiation therapy. Seventy six patients with breast cancer receiving external radiation therapy were followed longitudinally from the onset of treatment to 6 months post-treatment. Fatigue significantly increased over the course of treatment, was highest at the last week of treatment, and returned to pretreatment levels by 3 months after treatment. Fatigue was not influenced by the patient's age, stage of disease, time since surgery, weight, and length of time since diagnosis. Fatigue was significantly related to symptom distress, psychologic distress, and self-reported fatigue relief strategies. The most frequently reported self-relief strategies were "sit" and "sleep." Fatigue had a negative impact on the patient's quality of life. Impairment in quality of life was evident by the end of treatment, with improvement by 3 and 6 months after treatment. The second week through to the last week of radiation therapy are critical times to target interventions for the management of fatigue. The amelioration of concomitant symptoms is a supportive approach that might be helpful. Self-help strategies focusing on the cessation of activity and increasing rest were reported as successful by patients.