Radiotherapy (RT) is one of the three main pillars of modern cancer  treatment. For decades, RT has been predominantly performed with the  patient in supine or prone position. Positioning the patients in  upright, sitting or standing, position promises greatly reduced treatment cost, more patient comfort, and even anatomical advantages in  the form of reduced motion and greater separation of critical  structures. Since upright positioning enables smaller facility  footprints for photon therapy, and especially for particle therapy, it  is a key to global access to modern treatment options. It therefore  comes at no surprise that, with the commercial availability of upright  positioning solutions and upright volumetric imaging, upright  radiotherapy has enjoyed a surge in interest recently. At the same time,  key questions remain in urgent need of solutions, international  guidelines for upright positioning are lacking, and clinical workflow is  yet tailored to supine or prone positioning. As the first clinics  around the world are adopting upright technologies, there is a global  need for expert professionals in industry, clinics and research to bring  promised advantages from bench to bedside and carry this paradigm shift  in how RT patients are treated.