Upright multidetector CT (MDCT) enables whole-body, high-resolution, three-dimensional cross-sectional imaging in standing or sitting positions, providing detailed visualization of anatomy and biomechanics in physiologically relevant, load-bearing postures. This system maintains high spatial resolution and quantitative performance, including stable noise characteristics and consistent CT attenuation values, while improving workflow efficiency compared with conventional supine MDCT. In the shoulder and upper extremity, upright MDCT has clarified gravity-dependent alignment changes and enabled dynamic four-dimensional assessment of sternoclavicular and acromioclavicular joint motion. In the spine, it provides reproducible spinopelvic measurements, reveals posture-dependent narrowing of intervertebral foramina, and characterizes age- and sex-related differences in segmental spinal mobility. Upright MDCT of the knee allows precise evaluation of joint-line orientation, mechanical-axis migration, and rotational kinematics under weight-bearing conditions, enhancing diagnostic accuracy and preoperative planning in osteoarthritis. In the lower extremities, it captures kinetic-chain mechanics from the foot to the hip, integrating ground-reaction-force data to analyze load distribution and compensatory motion across adjacent joints. Upright MDCT also visualizes thoracic cage deformation and vertebral displacement in conditions such as pectus excavatum, demonstrating load-related changes that supine imaging may overlook. This review provides a state-of-the-art overview of upright MDCT applications in orthopedic imaging and highlights its potential to transform diagnostic strategies and deepen understanding of musculoskeletal pathophysiology under physiologically relevant weight-bearing conditions. Collectively, these studies demonstrate that upright MDCT is a quantitatively robust modality that offers new insights into functional anatomy, disease mechanisms, and biomechanical adaptation. By bridging diagnostic imaging with functional assessment, upright MDCT has the potential to refine understanding of musculoskeletal pathophysiology and to guide more personalized therapeutic strategies in orthopedic and related fields.