We investigated the relationship of caregivers' health-related quality of life (HRQOL) to the burden of caring for patients with Alzheimer disease (AD) and resource utilization. Caregiver HRQOL was assessed using the SF-12 Mental and Physical Summary scores. Compared with a normative, age-adjusted sample, the 2477 caregivers had lower mental and physical scores (for the latter, only those <54 years of age). Increased caregiver mental functioning was associated with caregiver support and perceived quality of patient medical care, fewer hours of caregiving, and fewer patient behavioral symptoms. The burden of caregiving has substantial effects on HRQOL. Interventions that improve AD status and reduce caregiving hours have the potential to improve caregivers' HRQOL.