This chapter discusses molecular targets for radiosensitization that have reached clinical trial or that are likely to form the basis of clinical trials in the future. The chapter explores several approaches to create radiosensitization through various interactions with EGFr. The receptor can be blocked by a specific antibody, such as cetuximab in the case of EGFr or trastuzumab in the case of Her2. Another approach is to interfere with the tyrosine kinase cytoplasmic component of EGFr, as is currently being explored with the small molecule gefitinib. Anti-EGFr-induced radiosensitization may also be intimately involved with DNA double-strand break repair. Angiogenesis inhibitors show considerable promise as possible synergistic agents for use with radiotherapy, which complements their potential systemic activity. Cetuximab and other agents targeting the EGFr appear to act in part through the anti-angiogenesis pathway, which may contribute to synergy with radiation. Various cell lines with Ras mutations have been shown to exhibit radioresistance. The first attempt to induce enhanced radiosensitivity through interference with the membrane binding of Ras was undertaken with lovastatin, a drug that non-specifically interferes with lipid metabolism. The importance of angiogenesis suggests that the standard measure of radiosensitization, the clonogenic assay, may be inadequate and more clinically relevant in vivo assays are required.