Opiates remain the choice of analgesia for severe pain despite numerous side effects. They possess the unique ability to alter the interpretation of noxious sensations normally sensed as pain, while leaving the sensations of touch, temperature, and proprioception essentially unchanged. Opiates act by mimicking naturally occurring endogenous peptides at a variety of receptors in the central nervous system (CNS). Disruption of pain sensation occurs because of the action of different opiate receptor types located along pain pathways in the CNS. Analgesic activity and adverse side effects of all narcotic analogs are directly related to the activity of the drugs at a combination of opiate receptors. The currently known opiate receptors (mu 1, mu 2, kappa, sigma, and delta) are described with respect to function and location along pain pathways. A brief description of nociceptive (pain) pathway anatomy is also presented. Application of knowledge has allowed the development of mixed agonist-antagonist drugs such as butorphanol (Stadol; Anaquest, Madison, WI/Bristol Meyers Squibb, Evansville, IN) that capitalize on specific opiate receptor activation or antagonism to decrease adverse side effects and abuse-dependence potential. Future research areas are discussed.