Opioid receptors belong to the large superfamily of seven transmembrane-spanning (7TM) G protein-coupled receptors (GPCRs). As a class, GPCRs are of fundamental physiological importance mediating the actions of the majority of known neurotransmitters and hormones. Opioid receptors are particularly intriguing members of this receptor family. They are activated both by endogenously produced opioid peptides and by exogenously administered opiate compounds, some of which are not only among the most effective analgesics known but also highly addictive drugs of abuse. A fundamental question in addiction biology is why exogenous opioid drugs, such as morphine and heroin, have a high liability for inducing tolerance, dependence, and addiction. This review focuses on many aspects of opioid receptors with the aim of gaining a greater insight into mechanisms of opioid tolerance and dependence.