Fatigue is one of the most common complaints of people with cancer. It affects the majority of patients actively undergoing cancer related therapies, but also a meaningful number of those who successfully completed therapy and are disease-free and potentially cured at the end of the treatments. In cancer setting, fatigue is to be defined as a chronic form of tiredness, which is perceived by the patient as being unusual or abnormal, and absolutely disproportionate with respect to the amount of exercise or activity he/she has carried out and which is not removed by resting or sleeping. The exact cause of fatigue is not known. In cancer setting there are many contributing or associated factors, such as cancer itself, cancer treatment (chemotherapy, radiation therapy, immunotherapy and surgery), depression or anxiety, some medications, pain, nausea, vomiting or diarrhea, poor nutrition, anemia, infections, insomnia. There is no standard of care for the assessment or treatment of fatigue in patients with cancer. The evaluation of fatigue is intrinsically multidimensional, even though the lack of objective measurement methods makes it difficult to draw up worldwide-accepted guidelines; nonetheless, a number of methods have been developed to assess it. Treatment of fatigue should depend on its cause, but presently it is still addressed against the associated symptoms rather than fatigue itself. Useful approaches includes erythropoietin alpha, psychostimulants, medications to treat pain, depression, nausea and difficult sleeping, physical therapy for reconditioning exercises or energy saving techniques, health education. In this report some of the crucial issues related to fatigue in people with cancer are reviewed.