Assessed the contribution of demographic, illness, and psychosocial parameters to the psychological adjustment of 64 caregivers of children with or at risk for HIV infection. As a group, caregivers reported a significantly greater level of psychological distress than the general population while the level of well-being reported by caregivers was similar to that of the general population. Illness and demographic parameters failed to significantly predict aspects of caregiver adjustment, together accounting for only six and nine percent of the variance in caregiver psychological distress and well-being, respectively. Psychosocial variables, however, contributed significant increments in the variance of both domains of caregiver adjustment. Specifically, higher levels of caregiver psychological distress were associated with poorer caregiver health status, greater number of coping strategies reported, and higher levels of family conflict. Higher levels of caregiver well-being were associated with perceptions of less impact of negative life events, lower levels of family conflict, and greater perceptions of emotional support. Implications for future research and intervention are discussed.