Abstract: Three recent technological advances have the potential to greatly improve the field of radiation therapy: proton beam therapy, image-guidance and inverse planning through computer optimization. Proton beams have a finite range and deposit most of their energy when they reach the end of that range. The characteristics make possible a substantial dose reduction to the normal tissues while maximizing the dose to the tumor. However, this finite range makes proton therapy dose distribution very sensitive to variations in tissue density in the beam path. The recent technological advances in imaging, especially the availability of four dimensional computed tomography (4DCT), allowed us to take consideration of the organ motion into the treatment planning process. Intensity-modulated radiation therapy (IMRT) is a novel technology that combines computer optimization of proton/photon pencil beams with most advanced treatment delivery technique to achieve the optimum radiation therapy for the cancer patients. In this talk, I will show how the 4D CT was used to design the proton treatment plan for the mobile tumors and mobile intervening anatomy. Our recent work by combining 4D CT, inverse optimization technique and deformable image registration algorithm will also be presented to show that the motion could actually benefit the radiation therapy if treatment plans are designed judiciously through optimization process.