It is now clear that there are three sub-types of the opiate receptor, mu, delta and kappa. Evidence for differential roles of these sub-types in pain modulation is accumulating since the advent of relatively selective agonists and more recently, antagonists for the three receptors. The actions of opioids in the spinal cord is reasonably well understood and there is increasing knowledge of supraspinal sites of action, peripheral analgesic effects in inflammatory states and in the interactions between opioid and non-opioid systems at spinal levels, which may start to explain some of the clinical states with altered opioid sensitivity.