Opioids acting through the μ opioid receptor traditionally represent the most effective analgesic agents. Alternatively, ligands acting as agonists at theδopioid receptor have been pursued as analgesic agents lacking the undesirable effects of m opioid agonists including morphine. This interest led to the development of selective peptide and non-peptideδligands, contributing to a better understanding of the physiological role of theδopioid receptor, including its interaction with other receptor systems. It is now understood that theδopioid receptors are involved in other biological processes, thereby providing tremendous therapeutic potential for agents acting at theδreceptor. Computer-aided modeling studies, in conjunction with pharmacological investigations of theδligands, have the potential to facilitate the exploitation of this potential via the development of predictive structure-activity relationships (SAR). To date, modeling studies have been performed on both peptidic and non-peptidicδligands, including conformational studies of constrained ligands, facilitating the identification of bioactive conformations ofδligands. In the present article, an overview of these modeling studies will be presented, with emphasis on the long-term goal of the development of therapeutic agents acting on theδopioid receptor.