Cancer-related fatigue (CRF) is a very common and distressing symptom experienced by most cancer patients, during and after treatments and also at the end of life. There is no accepted definition of CRF, because it is a multifaceted symptom that involves multiple biopsychosocial aspects. Several scales for assessing CRF have been used, unidimensional or multidimensional, but there is no agreement regarding the best instrument to measure CRF. Concerning the CRF treatment, pharmacologic and non-pharmacologic interventions have been used. Pharmacologic therapies have been evaluated in few randomized clinical trials: corticosteroids demonstrated a superior efficacy to the placebo in terminal cancer patients; psychostimulants (methylfenidate, dexamphetamine, modafinil), antidepressant (paroxetine), acetilcholinesterase inhibitors (donepezil), l-carnitine and coenzyme Q(10) generally have reported negative results. Non-pharmacologic interventions (physical exercise, psychosocial interventions and other integrative interventions, such as yoga, ginseng, acupuncture) have been evaluated in several randomized and non-randomized studies, but with many methodological limitations. Therefore, the most effective non-pharmacological intervention remains unclear and the effect sizes are small. Further research is needed to delineate the optimal definition, measurement and treatment of CRF.