The objectives of this study were to evaluate the impact of personal mastery and caregiving stress on caregiver depressive symptoms and health over time and to examine the moderating effect of mastery on the relations between stress and these outcomes. A total of 130 spousal Alzheimer caregivers completed yearly assessments of personal mastery, role overload, health symptoms and depressive symptoms. Random regression was used to evaluate the relations between time-varying values for stress and mastery in predicting depressive and health symptoms. It was found that variation in depressive symptoms over time was significantly related to role overload (p<0.05) and personal mastery (p<0.001). A significant overload-by-mastery interaction was found for predicting depressive symptoms (p=0.002) and caregiver health (p=0.008), whereby mastery attenuated the effect of stress on these outcomes. We conclude that personal mastery appears to reduce the effects of stress on depression and health outcomes over time.