This thesis explored significant other responses to CFS/ME in association with patient illness outcomes and symptom maintenance utilising a multi-method approach; a systematic review, cross-sectional, longitudinal and momentary methods were included. The review identified empirical evidence for two potential interpersonal mechanisms. The evidence suggested that significant other beliefs and responses, dyadic relationship quality, and patient outcomes associated with each mechanism were different. Dyadic belief incongruence was also highlighted as important with respect to relationship quality. Thus, potential research questions and current methodological limitations were identified; the subsequent empirical papers presented attempted to address these. The first empirical study (Chapter 3) utilised the Expressed Emotion (EE) framework to investigate the impact of critical comments and EOI; no cross-sectional associations between EE and patient outcomes were observed. A longitudinal design was also employed to examine the predictive validity of EE. Longitudinally, high critical comments predicted higher fatigue severity; further analyses indicated that depression mediated this relationship. High EOI was also predictive of higher fatigue severity at follow-up. This was the first study to examine EE within a CFS/ME sample; the longitudinal impact of high-EE upon patient outcomes suggests that it is a potentially beneficial target for future interventions. Paper 2 (Chapter 4) sought to examine the factors that might contribute to significant other EE by examining significant other illness beliefs and dyadic belief incongruence. The results indicated that significant others rated as high-EE had stronger illness models, more negative beliefs about the consequences associated with the condition, and negative emotional representations. These findings identify those beliefs that may be particularly important for high-EE within the current patient group. Overall dyadic belief incongruence was not important for EE-rating; high-EE dyads reported similar illness beliefs, whilst low-EE significant others reported more optimistic beliefs about the condition. These findings suggest that optimistic beliefs about the condition may be better for both significant other and patient outcomes. The final empirical study (Chapter 5) examined the associations between significant other negative and solicitous responses and fluctuations in patient illness outcomes on a momentary basis. The impact of significant other responses was largely transitory; changes in patient outcomes did not extend past the current momentary assessment. Negative significant other responses were associated with momentary increases in symptom severity; patient distress partially mediated this relationship. Patient-perceived solicitous responses were associated with increased activity limitation, but reduced disability reported at the same momentary assessment. These results suggest that momentary reports capture more dynamic processes than observed in traditional cross-sectional analyses. Taken together, the findings presented within this thesis provide further evidence for the impact of significant other factors on patient outcomes. The evidence for the hypothesised mechanism associated with critical EE was consistent throughout studies. However, the evidence for the role of EOI currently requires further exploration. Finally, the results suggest that the development of significant other-focussed interventions may be beneficial for both patient and significant other outcomes.