Fentanyl, a potent lipid-soluble opioid which was first synthesized more than 40 years ago, is still the most popular opioid used in the perioperative period throughout the world. Fentanyl's introduction, versatility, and popularity have resulted in its use in many acute and chronic pain conditions and a multitude of novel delivery systems in the last two decades. In spite of the development of more potent, safer, faster onset, and both shorter and longer lasting alternative opioids, fentanyl remains the mainstay of anesthesiologists and Certified Registered Nurse Anesthetists in the perioperative period, and for many pain physicians throughout the world.