Mental spatial reasoning is a ubiquitous skill in medicine. Medical students must learn the shapes and spatial relations of human anatomical structures; echocardiologists map dynamic 2D ultrasound images to their mental models of a three-dimensional beating heart; orthopedists visualize the biomechanics of joints and soft tissues moving and interacting; and surgeons must integrate information from medical images with their own anatomical knowledge to plan procedures and manipulate instruments. These mental visualization processes, which are engaged every day by medical professionals, have been extensively studied by cognitive scientists in the field of spatial cognition. Processes such as spatial visualization, mental rotation, perspective taking, cross-section visualization, and mechanical reasoning require conscious control and are cognitively demanding, placing a heavy burden on visuospatial working memory and executive functions. These mental skills also vary among individuals and within individuals according to experience. XR technologies have been developed to support and enhance these critical skills in medicine, and an understanding of the fundamental cognitive processes can support the effective design and use of these tools. This presentation will provide an overview of research on spatial cognition in medicine and will draw out implications for the design and implementation of XR technologies for both medical education and medical practice. Attendees will learn about fundamental constructs from the cognitive and learning sciences, to help guide design and implementation principles for XR tools that can unburden, rather than burden, cognition. By the end of this talk, attendees will have gained a theoretically and empirically grounded framework for understanding how XR technologies and human cognition form an interactive system for thinking, learning, and acting.