Chronic Fatigue Syndrome (CFS) is a condition characterised by severe mental and physical fatigue coupled with profound disability. The purpose of this review was to investigate psychological, social and physiological factors associated with fatigue and disability in CFS in children and adolescents. The review aimed to gain an overview of the strength of evidence for the relationship between these different factors and CFS in young people. Seventy-nine studies met the inclusion criteria and were included in the review. A narrative synthesis of these studies was conducted. The strongest and most consistent finding was that rates of psychiatric co-morbidity, predominantly anxiety and depressive disorders, were higher in young people with CFS compared to healthy controls or illness control groups. Studies suggested that many children and adolescents with CFS reported that their illness began with an infection and there was some objective and prospective evidence to support this. Preliminary evidence suggested a link between CFS and a family history of CFS, high expectations from both the parent and child, personality traits such as conscientiousness and physical illness attributions. The evidence was limited by methodological problems. Few studies were prospective in nature and future research should address this. Clinical implications of the findings are discussed and a hypothesised model of the factors associated with CFS in children and adolescents is presented.