Background and Objectives: Few population-based studies have directly compared caregivers of persons with dementia to caregivers of persons with other disabilities (nondementia caregivers). We enrolled dementia and nondementia caregivers who were providing substantial and sustained care and compared these groups on measures of caregiver stressors, appraisals of burden, and well-being. Research Design and Methods: Caregivers (N = 251) who provided continuous care for at least 1 year and at least 5 h per week were recruited from the population-based REasons for Geographic And Racial Differences in Stroke (REGARDS) study. Caregivers reported on dementia caregiving status, stressors, burden, and well-being. Results: Forty-seven percent (n = 117) reported caring for a person with dementia. Dementia caregivers reported more stressors, providing more care for self-care and behavioral problems than nondementia caregivers. Dementia caregivers also reported higher appraisals of stress and burden, and more depressive symptoms, but did not differ from nondementia caregivers on mental and physical health quality of life. In multivariable-adjusted models, adjustment for the total number of care recipient problems attenuated differences between dementia and nondementia caregivers on burden and depression measures. Discussion and Implications: Dementia and nondementia caregivers showed relatively few differences in indicators of overall well-being in this population-based sample, perhaps because both groups of caregivers in this study were providing substantial care. Dementia caregivers may require special assistance with dementia-specific problems such as behavioral problems. Clinical interventions and policy changes targeting highly burdened caregivers are needed to support them in allowing their care recipients to age in place at home.