Particle therapy is emerging as one of the promises of radiation oncology. Treatments of cancer patients with particle beams are increasingly becoming available worldwide. Proton and carbon ion beams create a unique pattern of dose deposition as a function of depth in tissue that can produce superior conformal dose distributions to the target volume when compared to conventional radiation treatments using megavoltage x-ray beams. Thus, the rationale for using particle beams clinically is the possibility of decreasing the total integral dose and sparing damage to the surrounding healthy tissues and critical organs, leading to higher doses to the tumor volume when compared to conventional radiation treatments. In addition, carbon ion beams are densely ionizing (“high LET) radiation exhibiting an increased biological effectiveness which makes them especially suitable for some radioresistant and hypoxic tumors. However, remarkably little is known about the type and complexity of DNA damage that particle therapies produce, which hampers our ability to exploit the full potential of particle therapy.