Recent advances in opioid therapy regarding routes of delivery, long acting preparations and sequential trials are described. Specifically the advantages and disadvantages of transdermal therapeutic system fentanyl, transmucosal fentanyl citrate, Kapanol TM and individual variability in the responses to different opioids are discussed in detail. Pain and the fear of pain are perhaps the greatest source of suffering. It is common sense to accept the fact of life that many diseases still cannot be cured, yet the accompanying suffering real. Hence relief is very important. Very few medications surpass opiods in terms of therapeutic efficiency, ease of application and lack of organic toxicity. The question is not whether opioids are effective but how to use them rationally. Many patients fail to have adequate analgesia, simply because doctors under-prescribe opioids as a result of lack of knowledge in their optimal usage.