Cancer pain is highly prevalent and often severe. Fortunately, most cancer pain can be readily managed, with up to 90% of patients responding well to standard interventions. However, breakthrough cancer pain-brief flares of severe pain superimposed on baseline pain-is common, difficult to manage, and often negatively impacts patients' quality of life. Breakthrough cancer pain is traditionally managed with oral, immediate-release opioids. However, because of its sudden onset and severity, oral opioids often fall short of providing adequate control. Research into novel approaches to pain management has identified several innovative strategies for this difficult cancer pain problem. We describe current approaches to assess, define, characterize, and treat breakthrough cancer pain, and summarize recent clinical research on novel agents, novel routes of drug delivery, and other advances in its management.