The modern practice of radiation therapy has developed over several decades, taking into consideration the anatomic location of the tumor, technical aspects of radiation delivery, combined treatment modalities, and patient comorbidity. Improved understanding of tumor biology and kinetics has resulted in a more intensive application of multimodality therapy for many forms of cancer in the endeavor to increase treatment efficacy. However, increased treatment intensity carries a risk of increased toxicity. Conversely, reduction of toxicity by lessening treatment intensity incurs the risk of reduced efficacy. Preventing or minimizing toxicity while maintaining or increasing efficacy is necessary for overall improvement in the therapeutic ratio. New methods for reducing toxicity are currently being explored and include identification of risk factors associated with increased toxicity, the development of radioprotectants, and the use of growth factors to accelerate the replacement of damaged cells.