In the Netherlands, a large-scale prospective cohort study was started on prolonged fatigue in the working population. The 1st issue that had to be addressed was the determination of a cutoff point for fatigue for use in the working population. Fatigue is measured with the Checklist Individual Strength (CIS), a 20-item self-report questionnaire. This article demonstrates the process of decision making in the determination of the cutoff point. Total CIS scores were calculated, sensitivity and specificity were compared for potential cutoff points, and a receiver operating characteristics analysis was conducted. A CIS total cutoff point for fatigue of >76 was determined, with a specificity of 90% and a sensitivity of 73%. Limitations regarding the use of cutoff points are discussed. It is concluded that the defined cutoff point seems to be appropriate for use in the working population.