Fentanyl, a short-acting synthetic pure opiate, offers an excellent option for the treatment of cancer and chronic pain. While oral administration is not an option, its high potency and lipophilicity have made intranasal administration feasible. Intranasal fentanyl has a bioavailability of 89%, with a short onset of action ( approximately 7 min) and duration times ( approximately 1 h). It bypasses the oral/gastrointestinal route, delivers the analgesic dose in a volume of 150 microl that can be adequately absorbed and, with a pH of 6.4, avoids local irritation. Intranasal fentanyl has been investigated to assess its potential as a well-tolerated acute postoperative breakthrough pain relief medication. It has been shown to be superior to oral transmucosal fentanyl for the treatment of cancer breakthrough pain. Similar analgesic effects to fentanyl or morphine intravenously and orally, with a similar safety profile, have been reported for postoperative or acute pain treatment of children and adults in the prehospital and hospital settings.