Chronic fatigue syndrome (CFS) is a medically unexplained illness characterized by persistent or relapsing fatigue lasting at least 6 months and producing substantial interference with normal activities accompanied by rheumatologic, infectious and neuropsychiatric complaints of similar duration (Fukuda et al., 1994). Prominent among these are cognitive difficulties including problems with information processing, learning, memory, and problem solving (Deluca, Johnson, & Natelson, 1993; Short, McCabe, & Tooley, 2002; Tiersky, Johnson, Lange, Natelson, & Deluca, 1997; Wearden & Appleby, 1997). Although impairments have been found in a variety of cognitive domains, the most robust findings in individuals with CFS are inefficient, slowed information processing in the verbal (Deluca, Johnson, Ellis, & Natelson, 1997) as well as visual domains (Deluca et al., 2004). Information processing is a basic cognitive component providing the underpinning for many other higher order cognitive functions including learning, memory, and problem solving. As speed of information processing decreases, the amount of information held at any one time in working memory, which stores and manipulates information, decreases (Wilhelm & Oberauer, 2006). Reduced working memory capacity can in turn affect an individual's ability to set decision making priorities, resolve conflicts, inhibit irrelevant information and make decisions appropriately, smoothly, efficiently, and cumulatively. These functions are subsumed under the term executive function, useful and often necessary for multi-tasking. Many individuals with CFS are challenged by multiple and competing input – leading to difficulties with multi-tasking especially under conditions of increasing complexity when there is a need to screen out irrelevant information. The development of the Attention Network Task (ANT) (Fan, McCandliss, Sommer, Raz, & Posner, 2002) is based on a well-developed neural network model of the human attention system (Fan et al., 2002; Posner & Petersen, 1990). The ANT combines a cued reaction time task (Posner, 1980) and a flanker task (Eriksen & Eriksen, 1974) and was developed to assess the operation of the attention system across three kinds of attention processing: alerting, orienting, and executive control (Posner & Petersen, 1990). The alerting condition of the ANT reflects the extent to which there is a benefit of temporal cueing to maintain cognitive vigilance. To assess orienting, a spatial cue is used before onset of the primary stimulus which reveals the efficiency with which subsequent targets can be located in space. Executive function is assessed by using peripheral or flanking arrows incongruent with a central target arrow that requires quick decision making, response coordination, and execution. We hypothesized that individuals with CFS would have significantly more difficulties (i.e., perform significantly more slowly) on the executive function component of the ANT when controlling for generalized slowing (measured using a simple reaction time task) consistent with previous findings (Deluca et al., 2004), using a different set of cognitive performance measures. In an earlier anatomical neuroimaging study, Lange et al. (1999) found CFS patients to have the most abnormalities in the frontal lobes – the region of the brain which includes a part of the executive control network. A functional neuroimaging study showed that activations of the alerting, orienting, and executive control networks were associated with the thalamic activations, parietal activations, and anterior cingulate cortex activations, respectively (Fan, McCandliss, Fossella, Flombaum, & Posner, 2005). Therefore, we also hypothesized that individuals with CFS would not have difficulties on the alerting and orienting component of the ANT when controlling for generalized slowing.