Chronic fatigue syndrome (CFS) is an illness characterized by disabling fatigue of at least 6 months. The aetiology of the condition has been hotly debated. In this chapter the evidence for CFS as a post viral condition and/or a neurological condition is reviewed. Although there is evidence that CFS is triggered by certain viruses in some patients and that neurobiological changes such as hypocortisolism are associated with the syndrome, neither mechanism is sufficient to explain the extent of the symptoms or disability experienced by patients. It is unlikely that CFS can be understood through one aetiological mechanisms. Rather it is a complex illness which is best explained in terms of a multifactorial cognitive behavioural model. This model proposes that CFS is precipitated by life events and/or viral illness in vulnerable individuals, such as those who are genetically predisposed, prone to distress, high achievement, and over or under activity. A self perpetuating cycle where physiological changes, illness beliefs, reduced and inconsistent activity, sleep disturbance, medical uncertainty and lack of guidance interact to maintain symptoms. Treatments based on this model including cognitive behavioural therapy and graded exercise therapy are effective at significantly reducing fatigue and disability in CFS. This chapter provides a description of these approaches and details of the trials conducted in the area.