Fentanyl is a lipophilic, short-acting, synthetic opioid with a piperidine chemical structure. Fentanyl is an effective analgesic for cancer pain, and newer formulations such as the transmucosal and buccal forms have shown efficacy for the management of cancer-related breakthrough pain. This article reviews the pharmacodynamics, pharmacology, and clinical efficacy for this new option in treating moderate to severe pain.