Disease-specific characteristics of pediatric illnesses may influence the functioning of families and the coping responses they enact. This study compared family functioning and coping styles within and between 2 different medical groups: families of children with cancer (n = 44) and HIV disease (n = 65). Most caregivers reported healthy family functioning, and no between-group differences in functioning emerged. However, with regard to coping, more reliance on social support was indicated among the cancer group. Also, the HIV group largely sought support from family, whereas both family and nonfamily support were sought among the cancer group. Better functioning was related to reframing, an active coping style, within the cancer group and passive coping within the HIV group. Thus, coping strategies and their implications for family functioning vary by condition. Researchers should avoid combining various illness groups indiscriminately. Likewise, clinicians should be sensitive to disease-specific factors when helping families learn to cope with illness-related stressors.