Radiation therapy is an essential component of cancer treatment. Currently, tumor control and normal tissue complication probabilities derived from a general patient population guide radiation treatment. Its outcome could be improved if radiation biomarkers could be incorporated into approaches to treatment. A substantial number of cancer patients suffer from side effects of radiation therapy. These side effects can result in treatment interruption. Such unplanned treatment interruptions not only jeopardize anticancer treatment efficacy but also result in poor post-treatment quality-of-life. To develop and translate radiation biomarkers for clinical use, NCI's Radiation Research Program, in collaboration with the Small Business Innovation Research Development Center, funded four small businesses through the request for proposals after peer review during 2015–2019. Here, we summarize publicly available information on intellectual property rights, the status of development, ongoing clinical trials, success in obtaining financing and regulatory approval. An analysis of publicly available information indicates all four companies have completed phase I of SBIR funding and advanced to further development, validation and clinical trials with phase II SBIR funding. These biomarkers are: 1. A panel of genomic biomarkers of radiation response to predict toxicity and radioimmune response (MiraDx Inc., Los Angeles, CA); 2. A multiplex assay for single nucleotide polymorphism (SNP) biomarkers of radiation sensitivity to identify a subset of prostate cancer patients for which radiotherapy is contraindicated (L2 Diagnostics, New Haven, CT); 3. A cell-free DNA assay in blood to measure tissue damage shortly after radiation exposure (DiaCarta Inc., Richmond, CA); and 4. A metabolomic/lipidomic assay to predict late effects that adversely affect quality-of-life among patients treated with radiation for prostate cancer (Shuttle Pharmaceuticals, Rockville, MD). This work also provides a bird's eye view of the process of developing radiation biomarkers for use in radiation oncology clinics, some of the challenges and future directions.