Introduction/background <p>Malignant tumors pose a serious threat to human health. As tumor volume increases, conventional external beam radiation therapy (cEBRT) faces challenges in tumor control and normal tissue toxicity. Spatially fractionated radiation therapy (SFRT) has emerged as an alternative approach.</p> Materials and methods <p>This article reviews the history of SFRT, including kilovolt X-ray based GRID, megavolt X-ray based GRID, MLC-shaped GRID, LATTICE radiation therapy (LRT), Bragg-peak based SFRT, microbeam, minibeam, SBRT-PATHY, and ISPART. It also explores its radiobiological mechanisms, such as immunomodulation, bystander and abscopal effects, and vascular response. Clinical studies of SFRT in palliative tumor treatment are summarized, and its limitations and future directions are discussed.</p> Results <p>SFRT has shown high symptom remission rates, significant target volume reduction, and even tumor control and long-term survival in some cases across various tumor types. However, it has limitations like lack of standardized dosimetric parameters, complex implementation, small-scale clinical studies, and uncertain immunomodulatory potential.</p> Conclusion <p>Despite limitations, SFRT shows promise as a palliative radiation therapy technique. Future large-scale, multi-center clinical trials are needed to standardize dosimetric parameters, clarify immunomodulatory mechanisms, and simplify the technology for wider application.</p>