Pregnant opioid dependent women have an increased risk of complications both during pregnancy and delivery. Substitution therapy can considerably reduce this risk. Unfortunately, this treatment is not without its side effects, often associated with neonatal abstinence syndrome (NAS), which requires treatment. Methadone and buprenorphine used as substitution therapy, mitigate extreme fluctuations in the concentration of opioids in the blood, which may occur during uncontrolled opioids abuse. The use of buprenorphine is associated with a lower risk of premature delivery, milder withdrawal symptoms and better neonatal health. However, women receiving buprenorphine discontinued therapy more often. Therefore, methadone is preferred in substitution therapy, especially in women who require higher doses of opioids in order to achieve homeostasis.