Breakthrough pain (BTP) is a transitory pain (reaching maximum severity in ~15 minutes and lasting ~60 minutes in patients with cancer) that occurs despite the management of chronic pain with long-term around-the-clock analgesia. BTP occurs in 33-65% of patients with chronic cancer pain and in ~70% of patients with chronic noncancer pain. BTP has historically been managed with short-acting opioids; however, these medications have a pharmacokinetic profile that does not correlate with the sudden onset and short time to maximum severity of BTP. Interest in rapid-onset opioids to relieve BTP has therefore been growing. This comprehensive review aims to summarize the currently available clinical data for the approved rapid-onset opioids, which comprise different formulations of fentanyl, a μ-opioid receptor agonist with anaesthetic and analgesic properties. Administration routes for fentanyl in the management of BTP currently include the transmucosal and intranasal routes; an intrapulmonary formulation is also in development. The findings of this review suggest that the efficacy and safety of the approved rapid-onset opioids are comparable.