Depression is the most common psychological sequela associated with stroke, affecting approximately 33% of stroke survivors (Hackett, Yapa, Parag, & Anderson, 2005) with corresponding impacts on spouses, partners, or other informal caregivers (Han & Haley, 1999; Low, Payne, & Roderick, 1999). Although stroke is more common in older persons, persons of all ages are at risk for stroke and especially post-stroke depression (Centers for Disease Control and Prevention [CDC], 2007; Barker-Collo, 2007; Hughes, Giobbie-Hurder, Weaver, Kubal, & Henderson, 1999). One of the factors which could explain increased risk of depression is "biographical disruption" (Bury, 1982), which happens when couples experience chronic illnesses that are developmentally off schedule or unexpected (Faircloth, Boylstei, Rittman, Young, & Gubrium, 2004; Pound, Gompertz, & Ebrahim, 1998; Roding, Lindstrom, Malms, & Ohman, 2003). The goal of this dissertation study was to examine modifiable factors associated with depression in stroke survivor-spouse dyads, including the potential moderating effects of biographical disruption. This goal was accomplished by pursuing three specific aims: (1) investigating the extent to which dyad-level factors are associated with current depression in stroke survivor-spouse dyads, above and beyond the influence of individual-level factors; (2) investigating the extent to which biographical disruption associated with stroke moderates the strength of association between individual and dyad-level factors and depression; and (3) exploring additional individual- and dyad-level features of disruption from stroke not included in the structured portion of the interview, and to explore how the experience of stroke may be different for couples in different developmental stages of life. Thirty-two recent stroke survivor-spouse dyads were interviewed using a combination of standardized measures and semi-structured interviews. Results showed that several dyad-level factors such as relationship quality, illness appraisal, and coping patterns were significant predictors of depression for survivors and spouses. The presence of biographical disruption did not statistically moderate these relationships, although the qualitative aspect of the study uncovered many aspects of disruption not addressed in the structured interview and the illness experience was clearly unique for couples in different developmental stages. These results have relevance for the development of effective interventions for post-stroke depression in couples, and are encouraging with respect to operationalizing and measuring the notion of biographical disruption from chronic illness across the lifespan.