It has been appreciated for some time now that humans react differently to opioids. A specific opioid such as morphine sulfate may have specific analgesic effects for certain patients with postherpetic neuralgia whereas in other patients with postherpetic neuralgia, it may provide quite different analgesic qualities. Also, in any one individual patient a particular opioid may provide better analgesia than other opioids. Furthermore, these differences are not unique to analgesia; they can also be seen with other opioid effects/toxicities. Though many of the differences can be classified neatly into pharmacokinetic and pharmacodynamic differences, there are certain differences which still remain incompletely understood. Also, clinicians are not yet able to easily predict which patients will respond well or poorly to various opioids. As research unravel the various genetics, biochemical, and receptor interaction differences of opioids in humans, it is hoped that easily obtainable, cost-effective testing will become available to aid clinicians in choosing an optimal opioid analgesic for an individual patient, a process which is currently accomplished via health care provider judgment along with trial and error. In the future, knowledge gained from databases on knockout rodents, pharmacogenetics, and gene polymorphisms may impact on the ability of clinicians to predict patient responses to doses of specific opioids in efforts to individualize optimal opioid analgesic therapy. It is conceivable that eventually information of this type may translate into improved patient care. In the future, armed with data of this type, clinicians may become quite adept at tailoring appropriate opioid therapy as well as optimal opioid rotation strategies.