In the past few decades, three-dimensional (3D) virtual simulation with computed tomography enabled more focused radiotherapy delivery such as intensity-modulated radiotherapy (IMRT), which delivers high dose to the target while simultaneously sparing nearby critical tissues. More recently, image guidance at the treatment sessions further promoted these advances in ensuring accurate localization of the target and reducing required setup margins. Cone beam computed tomography (CBCT), especially, has played an increasingly important role in contemporary image-guide radiotherapy (IGRT). With either megavoltage (MV) or kilovoltage (kV) x-rays, CBCT is so named because it utilizes a two-dimensionally collimated rectangular or cone-shaped beam and a flat-panel detector (FPD). It provides softtissue detectability for more precise target localization, and generates 3D images capable of treatment adaptation. New advances in CBCT technology correlate the images with respiration, enable image acquisition during the treatment, further improve the image quality, and reduce the imaging dose. Therefore, this important imaging modality has gained enormous popularity and is quickly replacing 2D based IGRT.