Breakthrough pain (BTP) in patients with cancer lacks a consensus definition and is subsequently inadequately diagnosed and assessed, therefore making it more challenging to manage. Cancer pain is generally moderate to severe in intensity and persistent in nature. Despite the problematic definition of BTP, it is generally described as having similar intensity, but may also be transitory and variable in predictability. Most breakthrough analgesia fails to be effective in the time required for BTP. No useful analgesia is therefore provided but drug adverse effects escalate. Cancer pain management relies on the WHO analgesic ladder. The frequency of BTP and its inadequate management means that it has significant adverse effects on patients, their families and those involved in their care. This article outlines a systematic, clinical and evidence-based approach to managing BTP in patients with cancer that emphasizes a holistic approach and an understanding of multidimensional 'total pain'. Guidelines for managing BTP are presented and areas of developing research are identified.