Fatigue is one of the most common complaints of people with cancer. In this 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. 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. The exact cause of fatigue is not known. There is no standard of care for the assessment or treatment of fatigue in patients with cancer. The evaluation of fatigue is intrinsically multidimensional, and 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. In this article some of the crucial issues related to fatigue in people with cancer are reviewed.