To examine the cross-national associations between familism and self-efficacy dimensions, and levels of burden and depression. Sociodemographic, familism, self-efficacy, depressive symptoms, and burden variables were measured in 349 dementia family caregivers from the US and Spain. US sample: greater support from family was positively related to self-efficacy for obtaining respite and self-efficacy for controlling upsetting thoughts and behaviors. Both self-efficacy constructs were negatively related to depression. Similar findings were obtained for burden. Spanish sample: higher scores on family as referents were associated with lower scores on self-efficacy for obtaining respite; lower scores on self-efficacy for obtaining respite were associated with higher depressive symptomatology. Study findings suggest that a significant interplay exists between the various facets of familism and self-efficacy, leading to differential caregiving outcomes. Unique cultural contexts and values derived from each country may exert distinct influences on how the caregiving role is perceived and appraised.