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Public health consequences of opioid dependence during pregnancy can only be inferred as increasing proportions of opioid-dependent women are addicted to non-medically prescribed analgesics and receive obstetrical care without being identified as addicted or treated. Because treatment recommendations for management of opioid dependence in pregnancy have primarily derived from studies in heroin-dependent pregnant women, there is a need to characterize and compare the clinical courses and complications of injection drug use (IDU) and non-medically prescribed opioids. Intrauterine overdose or withdrawal and the neonatal abstinence syndrome (NAS) may occur regardless of the route of opioid administration; whereas other obstetrical complications are likely consequences of poor prenatal care/self-neglect typical for IDU. Methadone maintenance compared to active IDU is associated with improved prenatal care, increased fetal growth, reduced fetal mortality, decreased risk of HIV infection, decreased risk of pre-eclampsia, decreased NAS and reduced foster care placement; however, significant NAS is still observed in >50% of these births. Benefits of methadone maintenance during pregnancy for addiction to non-medically prescribed opioid analgesics may be attributed to support, structure, and prenatal obstetrical oversight compared to the stressful and chaotic lifestyle of active addiction. While methadone has been the standard of care for >40 years, the Schedule III (methadone is Schedule II) partial opioid agonist buprenorphine merits examination in pregnancy because it has been found highly effective for treatment of opioid dependence, is associated with less severe withdrawal and is available in the U.S. under less severe restrictions than methadone. In the MOTHER study, maternal and neonatal outcomes of treatment with buprenorphine or methadone throughout pregnancy were compared in pregnant opioid-dependent women, in an international multi-center randomized, controlled, double-blind/double-dummy clinical trial (Jones et al., N Engl J Med 2010;363:2320-31). Although comparable numbers of methadone-exposed (57%) and buprenorphine-exposed (47%) babies required treatment for NAS, buprenorphine-exposed neonates required 89% less morphine to treat NAS; spent 43% less time in the hospital; and spent 58% less time in the hospital being medicated for NAS. The safety of opioid maintenance treatment during pregnancy must be judged in the context of comprehensive services (other than the administered medication per se) provided to addicted women by treatment programs. Buprenorphine is not inferior to methadone but may be preferable in terms of certain fetal outcome measures. Further research is needed to implement safe buprenorphine induction procedures in pregnant women, to balance reported teratogenic effects of opioids and benefits of opioid maintenance, and to determine the comparative safety and efficacy of methadone and buprenorphine for mother/fetus with co-occurring alcohol/benzodiazepine dependence or other psychiatric disorders and the psychoactiv medications used to treat them.