Recent advances in technology have led to dramatic improvements in radiation treatment planning, and delivery. These technical advances have allowed us to deliver higher radiation doses to the tumour while limiting dose to the normal surrounding tissues. Parallel advances in imaging and molecular biology have improved our ability precisely to define target volumes at risk, enhance radiation sensitivity, as well as to evaluate response to therapy. In this chapter, we will focus on the clinical improvements that have been achieved from both technological advances in radiotherapy (RT) planning and treatment delivery in combination with radiation response modifiers such as altered fractionation, chemotherapy, and molecularly targeted therapy.