Breakthrough pain is a transitory flare of pain occurring in most cancer patients against a background of otherwise controlled persistent pain. Treatment of breakthrough pain is a challenging phenomenon. Oral transmucosal fentanyl citrate (OTFC; brand name Actiq, Chephalon Inc., West Chester, PA), a new opioid formulation with a unique delivery system, reflects the characteristics of breakthrough pain (rapid onset of action and short duration), making it an effective treatment for cancer patients who already receive opioids and experience flares of pain. This review article aims to present the role of oral transmucosal fentanyl citrate in the management of breakthrough pain in cancer patients. In particular, it is going to discuss the synthesis, clinical pharmacology, pharmacokinetic and pharmacodynamic properties, toxicity, and clinical efficacy of this novel agent.