The OPRD1 gene encodes the delta-opioid receptor, which has multiple functions including regulating reward pathways. The gene contains more than 2,000 verified genetic variants but only 2 currently have evidence for specific functions: rs1042114 disrupts maturation of the receptor and rs569356 affects OPRD1 expression. These polymorphisms and others in the gene have been found to be associated with human diseases. The most reproducible data are associations between opioid addiction and three variants in intron 1 (rs2236861, rs2236857, and rs3766951), which have been described in a number of independent populations. Several publications also point toward an association between anorexia and a haplotype block containing rs569356 and rs533123. Unfortunately the mechanisms underlying these two effects are currently unknown. In contrast, rs1042114 has been linked to Alzheimer's disease through an increasingly well-defined mechanism by which the variant allele reduces production of the beta-amyloid plaques associated with the disease. Additional studies of OPRD1 variants are necessary to replicate current findings and to delineate the functional roles of relevant polymorphisms.