Transmembrane transport of endogenous as well as synthetic opioid peptides is a critical determinant of pharmacokinetics and biologic efficacy of these peptides. This transport process influences the distribution of opioid peptides across the blood-brain barrier and their elimination from the body. A multitude of transport systems that recognize opioid peptides as substrates have been characterized at the functional level, and these transport systems are expressed differentially at different sites in the body. Many of these transport systems have been identified at the molecular level. These include the H(+)-coupled peptide transporters PEPT1 and PEPT2, the adenosine triphosphate-dependent efflux transporters P-glycoprotein and multidrug resistance-related protein 2, and several members of the organic anion-transporting polypeptide gene family. There are however many additional transport systems that are known to transport opioid peptides but their molecular identities still remain unknown.