Although fatigue is a key component of the chronic fatigue syndrome, its definition and measurement remain relatively undeveloped. Most research on fatigue has been oriented towards work or performance of tasks and has involved laboratory studies of healthy individuals, while the study of fatigue as encountered in clinical settings has received minimal attention from investigators. This paper recommends that the natural history of chronic fatigue in its various clinical presentations be studied and that standardized assessment tools be used in this process. An investigation of the tools available for the assessment of fatigue yielded single-item, unidimensional, and multidimensional instruments. Additionally, the apparent association between affective illness and the chronic fatigue syndrome is addressed, and the fact that this relationship depends on issues of measurement is explored.