The discovery of endogenous opioids has begun an intricate saga involving multiple ligands and multiple receptors that form an extensive neuronal network in both the central and peripheral nervous systems. This intricacy is reflected in the complex pharmacology and diverse physiological effects of opioids in mammals. The aim of this chapter is to consolidate the immense literature on endogenous opioid ligands and attempt to rationalize the multiple forms of these bioactive substances. A number of recent reviews on endogenous opioids reflect different perspectives to this extensive field (Weber et al., 1983b; Frederickson, 1984; Akil et al., 1984; Offermeier and Van Rooyen, 1984; Imura et al., 1985; Herbert et al., 1985; Barchas et al., 1986).