This study used longitudinal data to examine the effects of spousal illness on depressive symptoms among middle-aged and older married individuals and the extent to which the adverse effects of illness in a spouse were mitigated by 2 psychological resources, mastery and self-esteem. Using 1,704 married participants who were 51 years of age on average, depressive symptoms were compared in 4 groups varying in their experience of spousal health transitions: those whose spouse remained ill at T1 and T2, those whose spouse declined in health from T1 to T2, those whose spouse's health improved from T1 to T2, and those whose spouse remained healthy at both time points. Mixed analyses of covariance showed that, as hypothesized, having a spouse who became or remained ill over time was linked to greater depressed affect by T2, whereas having a spouse improve in health was associated with a decline in depressive symptomatology. Moderated regression analyses indicated that while higher mastery and self-esteem were linked to lower depressed affect in general, these resources were especially protective against depressed affect for those whose spouse remained ill at both time points. These findings are at the intersection of life course theory and the stress process model highlighting the contextual forces in and the interconnectedness of individual development as well as the plasticity and resilience evident in adaptation to stress during mid and late life.