236The use of particle therapy for cancer treatment has become increasingly widespread and each year new particle (mostly proton) therapy facilities are built around the world. The interaction of particles with matter is fundamentally different from photons, resulting in distinct energy deposition patterns on the microscopic scale. Increasing the mass and charge of the irradiating particles results in a more concentrated distribution of energy deposition events in space. Accordingly, the extent of biological damage and response of the irradiated tissue may differ. For a given physical dose, particle irradiations are typically more effective than photon irradiation, and the concept of the relative biological effectiveness (RBE) was introduced to capture this effect. RBE is defined as the ratio of doses required to produce the same biological effect for reference (photon) and particle irradiations. In addition to the underlying difference in biological response, particle beams stop within the patient, producing highly conformal dose distributions. Most notably, particle beams have (nearly) no dose distal to the target. However, most of our clinical data is based on photon treatments. Relating experiences from photon treatments to particle therapy outcome modeling is thus not straight forward. In this chapter, we highlight the main differences of particle to photon therapy and how this impacts outcome modeling, we discuss important concepts for particle therapy and their potential applications.