Particle beams like protons and heavier ions offer improved dose distributions compared with photon (also called x-ray) beams and thus enable dose escalation within the tumor while sparing normal tissues. Although protons have a biologic effectiveness comparable to photons, ions, because they are heavier than protons, provide a higher biologic effectiveness. Recent technologic developments in the fields of accelerator engineering, treatment planning, beam delivery, and tumor visualization have stimulated the process of transferring particle radiation therapy (RT) from physics laboratories to the clinic. This review describes the physical, biologic, and technologic aspects of particle beam therapy. Clinical trials investigating proton and carbon ion RT will be summarized and discussed in the context of their relevance to recent concepts of treatment with RT.