Breakthrough pain (BTP) is experienced by many patients being treated with opioids for the management of chronic persistent pain. Control of BTP has been problematic since, until recently, the pharmacokinetics of older treatments was largely incompatible with the onset and duration of these pain episodes. Newer agents are now available that better approximate the timing of BTP episodes, and their use is increasingly being integrated into opioid-based pain management strategies. Successful management of BTP can improve treatment satisfaction and the quality of life of patients with chronic persistent pain of both cancer and noncancer origins. This article reviews the types of BTP, the therapeutic options available to manage BTP, and the tools designed to detect and minimize the risk of aberrant drug-related behaviors potentially associated with opioid medications.