Epidural injections in the cervical, thoracic, and lumbosacral spine have become important tools in the management of painful spine conditions. These injections should be carefully integrated into a comprehensive rehabilitation treatment plan. Well-controlled anesthetic and corticosteroid injections given with fluoroscopic guidance can help distinguish active pain generators from nonpainful structural abnormalities. This article presents various approaches and injection techniques that are used to selectively treat the tissues most often causing pain within and adjacent to the epidural space.