Antinociceptive effects and BBB transport properties of glycosylated enkephalin derivatives are reviewed. Previously, the application of enkephalins as analgesics has been retarded by their poor stability in vivo and by their inability to effectively penetrate the blood brain barrier. This shortcoming has been overcome by glycosylation, paradoxically leading to enhanced BBB transport via transcytosis. Principal design considerations required for enhanced binding, stability and transport of opioid peptides are reviewed. Modifications of the peptide backbone and side chains to achieve optimal receptor binding (micro/delta-selectivity) are presented. The importance of reversible binding between the glycopeptide and membranes is emphasized, and several pertinent examples of peptide-membrane interactions are discussed in the light of glycopeptide transport and opioid binding. An "amphipathic hypothesis" is introduced as a rationale for the observed BBB penetration of the opioid glycopeptides.