Post-exertional malaise is a cardinal symptom present in 95% of individuals with myalgic encephalomyelitis (ME/CFS). Repeated cardiopulmonary exercise testing has been momentous in revealing that the physiological systems of those with ME/CFS are impaired or damaged and do not respond to exercise/physical activity like those without the condition. The 24-h repeated exercise test may demonstrate a reduction in peak oxygen consumption (VO2 peak), VO2 at ventilatory threshold, power output at both peak and ventilatory threshold, along with a reduction/diminished maximal heart rate commensurate with chronotropic intolerance. In this chapter, I describe the process and methods of repeated cardiopulmonary exercise testing, used to assess exercise tolerance in individuals with ME/CFS.