The following case vignette outlines results from an assessment of a 38-year-old man diagnosed with chronic fatigue syndrome (CFS), a debilitating illness characterized by 6 or more months of severe, prominent fatigue, neurocognitive impairment, and physical symptoms such as recurrent sore throats, tender lymph nodes, multiple joint and muscle pain, weakness, exercise intolerance, unrefreshing sleep, and headaches. The case history describes a client who is highly demoralized as a result of having endured worsening CFS illness for the past 6 years. Central issues to be addressed in treatment include depressed mood, social isolation, cognitive impairment, irregular patterns of activity, and increased fatigue, nausea, and dizziness at morning time. The author invited leading researchers in the field of CFS to describe their proposed approaches to treatment following this case vignette.