Few studies have examined predictors of quality of life (QOL) of breast cancer survivors over time. Breast cancer survivors (n = 116) were asked to complete measures of QOL, mood, spirituality, and social support every 6 months from 2 to 4 years post treatment. Overall QOL at 4 years was predicted by previous physical and functional well-being, the breast cancer-specific items, and vigor and current levels of social support (Adj R (2) = .72, F = 30.53, p < .001). Physical QOL was predicted by previous levels of physical and functional well-being and current levels of functional and social/family well-being (Adj R (2) = .84, F = 44.30, p < .001). Functional well-being was predicted by prior levels of physical, functional, and social/family well-being and current levels of physical well-being and vigor (Adj R (2) = .72, F = 3-.53, p < .001). Emotional well-being was predicted by previous levels of emotional well-being and current physical well-being, the breast cancer-specific items, and anxiety (Adj R (2) = .60, F = 26.30, p < .001). Social/family well-being was predicted by previous levels of social/family well-being, social support, and confusion (Adj R (2) = .71, F = 34.18, p < < 000). The breast cancer-specific items were predicted by age, previous levels of the breast cancer-specific items, confusion, and current levels of emotional and functional well-being and spirituality (Adj R (2) = .58, F = 17.57, p < .001). Overall and specific dimensions of QOL at 4 years were predicted by different combinations of QOL, mood, and spirituality. Interventions should be tailored to which dimensions of QOL are affected and other types of QOL as well as social support, mood, and spirituality as coping mechanisms that influence the specific dimension of QOL affected.