This chapter discusses centrally acting analgesics-opioids. Natural opiates derived from poppy (somniferum) papaver. Natural plant alkaloids include morphine, codeine, and thebaine. Endogenous opioids are naturally occurring ligands for opioid receptor. Narcotic is a drug which induces narcosis or sleep. Opium contains more than 20 distinct alkaloids. This chapter covers the endogenous opioid system, opioid receptors, codeine, pethidine/meperidine, fentanyl, methadone, tramadol, agonist-antagonist, opioid antagonists, naltrexone, nalmephine, and nalorphine. The endogenous opioid peptides are derived from a distinct large precursor protein.