Phase I and II radiotherapy trials with accelerated high-energy heavy charged-particle beams have been carried out at the University of California Lawrence Berkeley Laboratory in conjunction with the Northern California Oncology Group and the Radiation Therapy Oncology Group. Clinical experience with several anatomical regions and tumor types has been accumulated. Preliminary observations suggest that toxicity is acceptable with treatment techniques developed for neon ions. Further data must be accumulated for carbon or silicon ion therapy. Initial Phase III trials with neon ions should begin shortly; evaluation of optimal ions and techniques for improved dose localization is ongoing. Future directions for optimization of heavy charged-particle radiotherapy are presented.