The use of ultra-high dose-rate ionizing radiation, termed FLASH irradiation (≥40 Gy/s), contributes to healthy tissue sparing while maintaining tumor control compared to conventional dose rate irradiation. This review summarizes current knowledge dedicated to studies of tumor and normal cell lines, animals including tumor-bearing ones irradiated in conventional and FLASH dose rate irradiation modes. As a comparison, data on FLASH irradiation with photons, electrons, protons, helium and carbon ions are also presented. The biophysical, molecular biological and immunological aspects of FLASH effect which are essential for understanding the radiation-induced processes in cells and tissues in order to improve radiotherapy of tumors are discussed.