The observation in 1979 that opioid receptors interact, led to the design of bivalent ligands in an attempt to improve selectivity and affinity towards the different subtypes (i.e. μ, δ and κ). Dimers of monovalent “parent” opioid structures have been evaluated and include: (a) endogenous (e.g. enkephalins) or exogenous (e.g. dermorphin) peptide dimer analogues (b) mixed peptidic-non-peptidic bivalent ligands and (c) dual non-peptidic dimers. Chimeric structures, using an opioid pharmacophore in combination with a non-opioid pharmacophore, have also been prepared. The common aim in all these studies is to improve the pharmacological profile of potential analgesics to minimize common opioid-induced side-effects, such as physical dependence and tolerance. Here we present a brief overview of efforts to develop bivalent opioid ligands for use in pain-related research.