Parental characteristics were significant predictors of health, functional abilities, and behavior problems in adults with Down syndrome (n = 75) over a 22-year time span, controlling for initial levels and earlier changes in these outcomes. Lower levels of behavior problems were predicted by improvements in maternal depressive symptoms. Higher levels of functional abilities were predicted by prior measures of and improvements in maternal depressive symptoms. Better health was predicted by prior measures of maternal depressive symptoms, paternal positive psychological well-being, relationship quality between fathers and their adult children, and improvements in maternal positive psychological well-being. Dementia status was also predicted by parental characteristics. The study suggests the importance of the family context for healthy aging in adults with Down syndrome.