This dissertation explores the experiences of people affected by symptoms associated with depersonalization/derealization disorder. This condition entails sensorial alterations resulting in a defamiliarization with the world and their bodies. The American Psychiatric Association, however, admits that depersonalization/derealization may be a part of meditative practices and should not, in certain cultural contexts, be diagnosed as a psychological disorder. Through a comparison of two distinct sensory cultures—communities of Vipassana meditation practitioners and patient-led communities—I explore the sense-making work that people perform to render destabilizing somatic sensations congruent with either medical or spiritual cultural worldviews. Drawing from personal narratives, online data, and psychiatric case studies, I argue that a sociocultural cosmic order, in which people ongoingly appraise sensory experiences in terms of their potential to foster “self-actualization,” largely determines whether social actors interpret these dissociative destabilizations as either pathological or aspirational—a process I term “sensory instrumentalization.” This comparative study adds to our understanding of how macro-level sociocultural arrangements may profoundly impact the subjective dimensions of experience. I contend that further exploring episodes of defamiliarization, which encompass instances in which social actors come to sense that the familiar world and their bodies are imbued with strangeness, may contribute to social scientists’ empirical and theoretical understanding of a tacit, sensory dimension of social experience.