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This paper explores the relationship between disability and quality of life and some of its implications for bioethics and healthcare. It focuses on the neglected perfectionist approach that ties well-being to the flourishing of human nature, which provides the strongest support for the common view of disability as a harm. After critiquing the traditional Aristotelian version of perfectionism, which excludes the disabled from flourishing by prioritizing rationalistic goods, I defend a new version that prioritizes the social capacities of human nature and the goods of personal relationship. This relationship-centered perfectionism is able to accommodate and explain disabled thriving. I also show how these issues have important implications for specific bioethical debates and clinical practices, using a cluster of issues related to Down syndrome as timely illustrations. My goal is to sketch a perfectionist theory that gives a more plausible account of the relationship between disability and well-being and that provides better practical guidance in cases involving judgments about the quality of disabled lives.