Metabolic reprogramming is a hallmark of cancer. Altered metabolism provides a survival advantage for cancer cells during tumorigenesis by supplying resources needed for uncontrolled growth and increased rates of cell division. As tumors grow beyond the limits of diffusion, altered metabolism provides a selective advantage in the context of nutrient deprivation. Many cancer therapies, including radiation, are known to impact tumor metabolism while the metabolic state of a cancer may contribute to radioresistance. Preclinical and clinical evidence exists to support combinations of radiation therapy with drugs that affect, for example, oxidative, glucose, glutamine, one-carbon, nucleotide, or iron metabolism in cancers. Work is ongoing to determine optimal strategies for combining these drugs with conventionally fractionated and hypofractionated radiation schemes. New strategies, including dietary manipulation during the course of radiation therapy, are currently being explored. Targeting tumor metabolism is a rapidly evolving and promising field of oncology and will be reviewed here in more detail.