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.