Povidone-iodine solution (Betadine) has long been accepted as an effective topical broad spectrum antiseptic, disinfectant, and tumoricidal agent. In colorectal operations, this solution generally has been used for the purpose of minimizing postoperative septic complications and reducing cancer recurrence, although the optimal application, advantages, and undesirable side effects have been debated. With limited prospective, randomized, controlled trials and insufficient data available, this article examines the safe and effective clinical applications of this solution for colorectal operations.