Substance abuse in pregnancy has increased over the past three decades in the United States, resulting in approximately 225,000 infants yearly with prenatal exposure to illicit substances. Routine screening and the education of women of child bearing age remain the most important ways to reduce addiction in pregnancy. Legal and illegal substances and their effect on pregnancy discussed in this review include opiates, cocaine, alcohol, tobacco, marijuana, and amphetamines. Most literature regarding opiate abuse is derived from clinical experience with heroin and methadone. Poor obstetric outcomes can be up to six times higher in patients abusing opiates. Neonatal care must be specialized to treat symptoms of withdrawal. Cocaine use in pregnancy can lead to spontaneous abortion, preterm births, placental abruption, and congenital anomalies. Neonatal issues include poor feeding, lethargy, and seizures. Mothers using cocaine require specialized prenatal care and the neonate may require extra supportive care. More than 50% of women in their reproductive years use alcohol. Alcohol is a teratogen and its effects can include spontaneous abortion, growth restriction, birth defects, and mental retardation. Fetal alcohol spectrum disorder can have long-term sequelae for the infant. Tobacco use is high among pregnant women, but this can be a time of great motivation to begin cessation efforts. Long-term effects of prenatal tobacco exposure include spontaneous abortion, ectopic pregnancy, placental insufficiency, low birth weight, fetal growth restriction, preterm delivery, childhood respiratory disease, and behavioral issues. Marijuana use can lead to fetal growth restriction, as well as withdrawal symptoms in the neonate. Lastly, amphetamines can lead to congenital anomalies and other poor obstetric outcomes. Once recognized, a multidisciplinary approach can lead to improved maternal and neonatal outcomes.