Density functional theory (DFT) has emerged as a powerful tool to model defect properties and dynamics at the quantum mechanical level. Results from targeted DFT calculations can provide valuable insight into the atomistic nature of radiation-induced defect phenomena in microelectronics. This review describes the foundations of DFT, its implementations, and defect calculations. Illustrative examples from recent studies are presented in which DFT calculations, combined with experiments, have led to new insights into the microscopic processes that lead to the observed radiation response. These include GaN/AlGaN HEMTs, proton-induced interface-trap formation at the interface, and the role of hydrogen in enhanced low-dose-rate sensitivity (ELDRS) in bipolar devices and ICs.