Objectives. This study examined the association between caregiving for disabled or ill family members, estimated to occur in more than 22 million US households, and change in mental health. Methods. We assessed 4-year change in mental health among 37 742 Nurses' Health Study participants with the Medical Outcomes Study Short-Form 36. Results. Women who provided 36 or more weekly hours of care to a disabled spouse were almost 6 times more likely than noncaregivers to experience depressive or anxious symptoms (multivariate odds ratio [OR] = 5.6; 95% confidence interval [Cl] = 3.8, 8.3). Caring for a disabled or ill parent (≳36 weekly hours) was associated with a less dramatic elevation in depressive or anxious symptoms (multivariate OR=2.0; 95% Cl = 0.9, 4.3). Conclusions. In this population, caregiving was associated with increased risk of depressive or anxious symptoms.