The neurobiology of the endogenous opioid system, as well as related neurobiology of opiate addiction, the treatment of addiction, and the management of pain, covers an area of scientific research that has been unfolding over the past 40 years, with increased clinical and laboratory-based information. Between 1992 and 1994, researchers had clearly defined three types of opioid receptors (, , and ) using selective chemical ligands. The challenge to clone the receptor genes was not met until late 1992, at which time two groups working independently in Los Angeles, California, and Strasbourg, France (respectively, the groups of Evans and Kieffer), first cloned an opioid receptor from a neuronal cell line known to have opioid receptor activity. Soon thereafter, the genes were cloned for the specific and opioid receptors, first in rodents, then in humans. Especially rapid advances have been made since the first successful cloning of the genes of the endogenous opioid receptors in late 1992 (e.g., Chen et al. 1993a, 1993b; Evans et al. 1992; Kieffer et al. 1992; J. B. Wang et al. 1993) and many laboratories have written extensive scientific papers on both the early and more recent advances, along with pertinent review articles (Kreek 1986, 1987, 1992, 1996a, 1996b, 1996c, 1996d, 2000a, 2000b, 2001, 2002, 2003, 2005; Kreek and Koob 1998; Kreek et al. 2002, 2004a, 2004b, 2005a, 2005b; LaForge et al. 2000; Novick et al. 1991). There are also many exciting review articles from 2001 onward that may be used to identify more specific scientific papers on the neurobiology of the opioids (Borgland 2001; Contet et al. 2004; Corbett et al. 2006; Cox and Crowder 2004; Evans 2004; Johnson et al. 2005; Kieffer and Evans 2002; Kieffer and Gaveriaux-Ruff 2002; Law et al. 2004; Maher et al. 2005; Nestler 2004, 2005; Ossipov et al. 2005; Pan 2005; Pasternak 2001; Qui et al. 2003; Raehal and Bohn 2005; Snyder 2004; Williams et al. 2001; Zadina 2002).