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For many millions of users, 3D virtual worlds provide an engaging, immersive experience heightened by a synergistic combination of visual realism with dynamic control of the user’s movement within the virtual world. For individuals with visual or dexterity impairments, however, one or both of those synergistic elements are impacted, reducing the usability and therefore the utility of the 3D virtual world. This article considers what features are necessary to make virtual worlds usable by such individuals. Empirical work has been based on a multiplayer 3D virtual world game called PowerUp, to which we have built in an extensive set of accessibility features. These features include in-world navigation and orientation tools, font customization, self-voicing text-to-speech output, key remapping options, and keyboard-only and mouse-only navigation. Through empirical work with legally blind teenagers and adults with cerebral palsy, these features have been refined and validated. Whereas accessibility support for users with visual impairment often revolves around keyboard navigation, these studies emphasized the need to support visual aspects of pointing device actions too. Other notable findings include use of speech to supplement sound effects for novice users, and, for those with cerebral palsy, a general preference to use a pointing device to look around the world, rather than keys or on-screen buttons. The PowerUp accessibility features provide a core level of accessibility for the user groups studied.