Opioid receptors are members of the superfamily of the seven transmembrane G protein-coupled receptors (GPCRs). They were initially recognized as three distinct entities in the late 1970s and early 1980s on the basis of pharmacological studies that demonstrated differential distribution and binding of endogenous and synthetic ligands (1,2). However, their molecular characterization was only possible after the cloning of the three distinct cDNAs for δ, μ, and κ opioid receptors in the early 1990s (3–7). The predicted amino acid sequence for the different opioid receptors led to the identification of several structural characteristics that are shared among members of the GPCR receptor superfamily. They contain an extracellular N-terminus, seven hydrophobic transmembrane domains (TM1-7), connected by relatively short intracellular and extracellular loops, and a short intracellular C-terminal tail. Comparison of their deduced protein sequences revealed that opioid receptors are about 60% identical, with the greatest identity found in the transmembrane domains (73–76%) and intracellular loops (86–100%) (3). Despite these similarities, δ, μ, and κ opioid receptors bind specific ligands with different affinities. Furthermore, ligand binding induces conformational changes of the receptors leading to the activation of the G_i/G_o proteins and consequently very specific cellular responses. Each of the steps of opioid receptor function: ligand binding, conformational changes, and coupling to trimeric G proteins can represent an important point of regulation of the receptor function.