Modern interventional radiology practice is continuously evolving. Developments include increases in the number of central venous catheter placements and tumor treatments (uterine fibroid therapy, radio- and chemoembolization of liver tumor, percutaneous radiofrequency and cryoablation), and new procedures such as abdominal aortic aneurysm stent-graft repair, vertebroplasty, kyphoplasty, and varicose vein therapies. There have also been recent advancements in standard biliary and urinary drainage procedures, percutaneous gastrointestinal feeding tube placement, and transjugular intrahepatic portosystemic shunts. Prophylactic antibiotics have become the standard of care in many departments, with little clinical data to support its wide acceptance. The rise in antibiotic-resistant strains of organisms in all hospitals worldwide have forced every department to question the use of prophylactic antibiotics. The authors review the evidence behind use of prophylactic antibiotics in standard interventional radiology procedures, as well as in newer procedures that have only recently been incorporated into interventional radiology practice.