In recent years a better understanding of the pharmacologic and pharmacokinetic properties of methadone, including equianalgesic ratios has led to its increased use as a second line opioid for the treatment of pain in patients with cancer. Methadone may be an important alternative for those who have side effects related to the use of other opioids because it has no known active metabolites, is well absorbed by oral and rectal routes, and also has the advantage of very low cost. However, it has a long, unpredictable half-life, which can result in accumulation and toxicity in some patients. In addition, rotation to methadone as a second line agent is more complex than with other opioids because of its increased potency in those patients who are opioid tolerant, particularly those who have been on higher doses of other opioids. Future research should address the use of methadone as a first-line agent in the management of cancer pain, its use in patients with neuropathic pain, and in those who develop rapid tolerance to other opioids. In some patients with cancer the long half-life of methadone offers the advantage of extended dosing intervals to 12 and even 24 hours, further research is also needed in this area.