Early research on stress typically adopted models assuming that events themselves serve as the causal agent behind pathology, illness, maladaptive behavior, and other unhealthy outcomes. In contrast to environmental models, psychological models of stress have emphasized the perception of threat in response to specific environmental demands, coupled with a second-order appraisal of one's ability to cope with the demand (Benight & Bandura, 2004; Lazarus, 1999; Lazarus & Folkman, 1984). Despite agreement around this general conceptualization, from which the construct of “perceived stress” emerged (Cohen, Kessler, & Gordon, 1995), the critical constructs underlying perceived stress have been more challenging to identify. Approaching this challenge, Cohen and colleagues (Cohen, Kamarck, & Mermelstein, 1983; Cohen & Williamson, 1988) developed the Perceived Stress Scale (PSS) to assess the extent to which individuals globally find their lives to be unpredictable, uncontrollable, and overloaded. Factor analyses tended to find two factors, one reflecting unpredictable-uncontrollable-overloaded appraisals, and another seeming to tap into confidence in executing an appropriate coping response (e.g., Golden-Kreutz, Browne, Frierson, & Andersen, 2004; Sharp, Kimmel, Kee, Saltoun, & Chang, 2007). Although their factor analyses indicated the presence of two factors, some of these researchers attributed the separation between these two factors to semantic (i.e., positively vs. negatively worded items), rather than conceptual differences (Cohen & Williamson, 1988; Gonzalez Ramirez & Landero Hernandez, 2007; Mimura & Griffiths, 2008; Siqueira Reis, Ferreira Hino, & Rodriguez-Anez, 2010). Thus, subsequent research using the Perceived Stress Scale (PSS) has overwhelming treated perceived stress as a monolithic construct. An alternative approach to understanding the dimensionality of perceived stress was proposed by Levenstein and colleagues, who developed the Perceived Stress Questionnaire (PSQ; Levenstein et al., 1993) by selecting items tapping potential cognitive, emotional, and symptomatic sequelae of stressful events. Because they viewed affect and psychosomatic conditions—e.g., feeling rested, feeling discouraged, being lighthearted—as triggers of subsequent symptomatology and reflective of perceived stress, rather than as symptoms themselves, the dimensions of perceived stress underlying the PSQ differ from the PSS. Psychometric studies have found a variety of factors reflected in the PSQ, including worries, tension, joy, demands, and fatigue (Fliege et al., 2005; Levenstein et al., 1993). The PSQ and the PSS both show strengths in predicting physiological (Cohen & Williamson, 1988; Fliege et al., 2005; Levenstein et al., 1993; Remor, Penedo, Shen, & Schneiderman, 2007) and psychological (Cohen et al., 1983; Crowe et al., 2011; Levenstein et al., 1993; Pedrelli, Feldman, Vorono, Fava, & Petersen, 2008) outcomes that one would expect to follow from stress. What remains unanswered, however, is why the stories they tell about the constructs underlying perceived stress appear to be so different. The lack of a clear answer to this question suggests that further investigation of the dimensionality of perceived stress is warranted. A better understanding of what is actually being measured can help elucidate the reasons why perceived stress is such a potent predictor of pathology, and whether this relationship is a consequence of global or specific aspects of stress appraisal. The Current Study We sought to better understand the factors underlying perceived stress. Items designed to measure this construct were administered every 4 weeks (13 times total) to participants diagnosed with multiple sclerosis (MS). These items included the entire PSS as well as 16 items drawn from the PSQ that were selected to avoid confounding with symptoms of chronic illness (e.g., fatigue) or psychopathology (e.g., anhedonia), as these constructs are common endpoints in stress research. This approach permitted comparisons of the dimensions of perceived stress offered by several alternate models. A priori, we aimed to use confirmatory factor analysis (CFA) to replicate the one-dimensional and two-dimensional solutions to the PSS described above and determine their validity in our population. Next, exploratory factor analysis (EFA) of the 10-item PSS permitted us to see if the solutions reported in previous studies were the most appropriate ones for our population. Finally, we aimed to construct a new measure of perceived stress with improved breadth and structural validity, by deriving a novel solution using the combined 26-item set of indicators. To examine the validity of these different solutions, we compared correlations between the factor-derived subscales and constructs relevant to concurrent validity (i.e., depressive and anxiety symptoms, health services utilization, stressful events) across the different models. We also examined stability of the competing models over time.