Cancer-related pain is a common clinical problem, experienced by ∼90% of patients with cancer. The mainstay of treatment remains opioids and the WHO analgesic ladder. Following the principles of the analgesic ladder, 80% of patients can achieve pain control. However, breakthrough pain remains a form of cancer-related pain that is particularly difficult to manage in both specialist and generalist settings. The focus of this article is the mismatch between the temporal characteristics of the majority of cancer-related breakthrough pain which is fast onset and resolution, with the pharmacological profile of oral morphine. The contribution of fast-acting fentanyl preparations to the treatment of breakthrough pain and the evidence for the various commercially available preparations will be considered.