Childhood chronic illness is replete with stressors that affect children's functioning across physical, social, emotional, and psychological domains. In this project, efforts were directed toward the identification and assessment of spirituality as a potential addition to the approach-avoidance paradigm of coping response. Twenty-two children diagnosed with either cancer or sickle cell disease were interviewed, along with their mothers, regarding psychosocial adjustment and typical approaches to coping with stressors. Children completed depression, anxiety, and quality of life questionnaires. Child participants were also asked to rate how often they utilized specific spiritual and general coping strategies in the month prior to the assessment. Mothers completed measures of depression and spiritual well-being, as well as parent proxy reports on their children's quality of life and use of spiritual coping. A factor analysis of the spiritual coping measure designed for use in the study (the Spiritual Coping Module) indicated strong support for the theoretically driven factors of religious and existential coping. Children's use of coping did not significantly account for heightened quality of life, nor for the presence of depressive and anxious symptomatology. However, maternal spiritual well-being accounted for 52.5% of the variance in self-reported maternal depression. Results are discussed in the context of improving children's adjustment to chronic illness through increased understanding of the child's and family's pattern of coping responses.