Purpose: Owing to the coronavirus disease 2019 (COVID-19) pandemic, radiation oncology departments have adopted various strategies to deliver radiation therapy safely and efficiently while minimizing the risk of severe acute respiratory syndrome coronavirus-2 transmission among patients and health care providers. One practical strategy is to deliver stereotactic body radiation therapy (SBRT) in a single fraction, which has been well established for treating bone metastases, although it has been infrequently used for other extracranial sites. Methods and Materials: A PubMed search of published articles in English related to single-fraction SBRT was performed. A critical review was performed of the articles that described clinical outcomes of single-fraction SBRT for treatment of primary extracranial cancers and oligometastatic extraspinal disease. Results: Single-fraction SBRT for peripheral early-stage non-small cell lung cancer is supported by randomized data and is strongly endorsed during the COVID-19 pandemic by the European Society for Radiotherapy and Oncology-American Society for Radiation Oncology practice guidelines. Prospective and retrospective studies supporting a single-fraction regimen are limited, although outcomes are promising for renal cell carcinoma, liver metastases, and adrenal metastases. Data are immature for primary prostate cancer and demonstrate excess late toxicity in primary pancreatic cancer. Conclusions: Single-fraction SBRT should be strongly considered for peripheral early-stage non-small cell lung cancer during the COVID-19 pandemic to mitigate the potentially severe consequences of severe acute respiratory syndrome coronavirus-2 transmission. Although single-fraction SBRT is promising for the definitive treatment of other primary or oligometastatic cancers, multi-fraction SBRT should be the preferred regimen owing to the need for additional prospective evaluation to determine long-term efficacy and safety.