As the volume of cancer survivors continues to increase, clinicians are being faced with a growing number of patients with cancer-related fatigue (CRF). Survivors with a variety of malignancies may experience fatigue. Many potential barriers to the identification of this symptom in a cancer survivor may exist, due in part to both the patient and the clinician. Assessment of patients for fatigue is important because it can profoundly effect their daily lives. Many factors contribute to CRF. Hence, the clinician may face a daunting challenge in attempting to alleviate CRF. Treatment modalities for CRF include nonpharmacologic interventions, such as psychosocial interventions, exercise, sleep therapy, and acupuncture. Pharmacologic interventions include stimulants, namely modafinil and methylphenidate. In some patients antidepressants may be beneficial. Clinicians should assess cancer survivors for the presence of fatigue and focus on its treatment in an attempt to ensure that these patients have the best possible symptom control.