Fluoroscopy and computed tomography (CT) guidance for interventional procedures can provide clear vision of the targets. However, ionizing radiation during fluoroscopy and CT-guided procedures can cause serious damage to both patients and medical professionals, including skin lesions, cataracts, cancer, and teratogenic effects on fetus and genetic mutations. In spite of the potential radiation damages, recent studies show that worldwide physician interests and knowledge on radiation safety and appropriate use of radiation protection are lacking. More education and training are needed to enhance the physician awareness of radiation safety. Techniques such as utilizing less fluoroscopy time, increasing the distance from the radiation source, using pulsed fluoroscopy, lower dose, and collimation have been proven to decrease radiation exposure. Appropriate utilization of radiation protection equipment including under-table shield, mobile shield, and apron can potentially minimize the professional radiation exposure close to 0 even when hundreds of fluoroscopy-guided procedures are performed monthly. Techniques such as performing proper preprocedure planning, performing CT fluoroscopy intermittently, modifying the longitudinal scan length, number of scans, and tube current-exposure time can all minimize the radiation dose in CT-guided procedures. Development of surgical techniques such as a computer-assisted navigation for pedicle screw placement and stereotactic guidance system under fluoroscopy may further decrease radiation exposure to both patients and physicians. More research on ultrasound-guided spine procedures may bring a new technique to deliver the medications safely and accurately to the patients without any risks of ionizing radiation.