Highly conformal radiation therapy tailors treatment to match the target shape and position, minimizing normal tissue damage to a greater extent than previously possible. Technological advances such as intensity-modulated radiation therapy, introduced a decade ago, have yielded significant gains in tumor control and reduced toxicity. Continuing advances have focused on the characterization and control of patient movement, organ motion, and anatomical deformation, which all introduce geometric uncertainty. These sources of uncertainty limit the effectiveness of high-precision treatment. Target localization, performed using appropriate technologies and frequency, is a critical component of treatment quality assurance. Until recently, the target position with respect to the beams has been inferred from surface marks on the patient's skin or through an immobilization device, and verified using megavoltage radiographs of the treatment portal. Advances in imaging technologies have made it possible to image soft tissue volumes in the treatment setting. Real-time tracking is also possible using a variety of technologies, including fluoroscopic imaging and radiopaque markers implanted in or near the tumor. The capacity to acquire volumetric soft tissue images in the treatment setting can also be used to assess anatomical changes over a course of treatment. Enhancing localization practices reduces treatment errors, and gives the capacity to monitor anatomical changes and reduce uncertainties that could influence clinical outcomes. This review presents the technologies available for target localization, and discusses some of the considerations that should be addressed in the implementation of many new clinical processes in radiation oncology.