Combinations of the chemotherapy and radiation therapy are increasingly a part of treatment strategies for cancer. Although directed at distant metastasis, they may have little effect on the primary tumor and regional lymph nodes. The local tumor must be controlled to 1) eliminate life-threatening complications, 2) decrease the risk of distant metastasis, and 3) permit organ conservation. Induction chemotherapy has been shown to be effective in decreasing distant metastasis, but it does affect local tumor control in common epithelial tumors. Concurrent single agent chemotherapy can increase local control with radiation therapy and combination chemotherapy concurrent with irradiation can both improve local control and decrease distant metastasis. Combination chemoradiation therapy has become a major part of research strategies of the Radiation Therapy Oncology Group (RTOG): it has been shown to improve local control and survival in carcinomas of the esophagus and nasopharynx. Combination chemoradiation has increased organ conservation in carcinoma of the anal canal and it is under investigation for carcinomas of the larynx (laryngeal preservation), other head and neck sites, lung, and cervix. The equation--increased local tumor control + decreased distant metastasis = increased survival--is the paradigm. Systemic therapy with cytotoxic drugs or hormones needs to address both potential sites of failure.