The description of multiple classes of opioid receptors has had a major impact on our understanding of the mechanisms of analgesia. Three major classes of opioid receptors have been defined: mu, kappa, and delta. The mu receptors have been further subclassified into two distinct subtypes (mu 1 and mu 2), as have the delta receptors (delta 1 and delta 2). Kappa receptors have been subdivided into kappa 1, kappa 2, or kappa 3 subtypes. All of these subtypes modulate pain perception, with the exception of the kappa 2 receptor, which has not been adequately examined. Supraspinal systems have been described for mu 1, kappa 3, and delta 2 receptors while mu 2, kappa 1, and delta 1 receptors modulate pain at the spinal level. In addition to their ability to act independently, the various systems also interact synergistically with each other. Thus, the relief of pain involves the complex interaction of at least six receptor systems. This review discusses the implications of opiate receptor multiplicity on the control of pain.