Corticosteroids and local anesthetics are some of the most commonly administered medications in radiology departments. These medications have marked variability in their formulations, which may increase their adverse event profile for specific procedures. In particular, certain corticosteroid preparations are associated with adverse central nervous system (CNS) sequelae. This is most likely due to distal embolization by particulate formulations. Nonparticulate steroid formulations are not associated with such events. Local anesthetics have severe CNS and cardiac adverse effects if injected intravascularly and have recently been associated with intraarticular chondrolysis if used in large doses. This review discusses these medications with particular emphasis on their established and postulated adverse effects. The administering radiologist should be aware of these potential effects and how best to reduce their occurrence.