The cloning of the mu, delta and kappa opioid receptor genes in the early 1990s has allowed the genetic determinants that control the expression of each opioid receptor to be dissected. Regulation of these genes involves transcriptional and post-transcriptional events. At the transcriptional level, most recent studies have revealed both positive and negative roles for various transcription factors, vitamin A hormones and cytokines in opioid receptor gene regulation. Post-transcriptional events involve alternative splicing and variation in mRNA stability and translation efficiency of these gene transcripts. Reports have also shown polymorphisms of the mu opioid receptor gene, primarily in the regulatory region, suggesting a potential connection between this gene and the likelihood of opioid abuse in humans.