Although prolonged or chronic fatigue is a very common complaint in primary care medicine, a biomedical obvious cause is often not found. In such a case, for women between 18 and 50 years with a ferritin level of less than 50 µg/l in the absence of anaemia, an iron supplementation may be associated with an improvement in fatigue. Appropriate treatment is also important for depression, anxiety or insomnia. In other cases, the approach is essentially non-pharmacological in the form of lifestyle advice, empathy and cognitive behavioural therapy as well as progressive and adapted physical exercises.