With the development of megavoltage treatment and computerized treatment planning the quality and precision of radiation oncology has steadily improved. Likewise, these developments have contributed to better local control for some cancers; however, micrometastatic lesions beyond the radiation treatment field and ineffective systemic treatments for many malignancies hamper efforts at the most important oncological end point, survival. Major advances in cancer therapy are therefore likely to come with improved combined modality treatment representing integration of local modalities with the systemic. These advances, in our opinion, will come from biological developments that address the problems that the modern oncologist faces at the cellular level. The biological developments will incorporate modern molecular biology, continued probing for biochemical mechanisms, and an intensified effort to learn more about the complexities of human tumor physiology.