Despite advances in symptom management, patients commonly experience fatigue during radiation therapy (RT). Minimal research has been conducted to determine how evidence-based recommendations are put into clinical practice and used by patients to manage fatigue. The aims of the current study were to identify the self-care strategies used by patients receiving RT, explore the effectiveness of those strategies, and identify how patients learned about fatigue management. Participants reported using multiple recommended interventions to relieve fatigue. The majority of participants reported they primarily rested or slept to improve fatigue. They also reported decreasing their activity level, exercising, using stimulants and complementary therapies, and eating and drinking nutritious items. More than half of the participants reported some relief of fatigue regardless of the intervention used. The majority of participants reported that they learned how to manage their fatigue mostly through experience and trial and error. Nurses need to explore the complex dynamics of each patient's fatigue and tailor multiple evidence-based interventions to maximize each patient's functional status and quality of life. When assessing and teaching about fatigue, nurses need to explore patients' daytime activity level and daytime sleep to be sure that excessive inactivity is not contributing to fatigue.