Combined modality therapy using both chemotherapy and radiation has proved superior over radiation therapy alone for a variety of cancer types. While the locoregional control and survival benefits have been established, there is still much room for improvement both in terms of cancer control and normal tissue toxicity, i.e. the therapeutic ratio. Recently, the pace of research and development of both conventional cytotoxic and molecularly targeted radiosensitizers has been staggering. The aim of this paper is to bring the reader up to date on the clinical status of four promising new radiosensitizers: novel camptothecin analogs and inhibitors of poly(ADP-ribose) polymerase, histone deacetylase, and heat-shock protein 90.