Maternal antidepressant use has increased during the past 2 decades, with venlafaxine emerging as a common agent during pregnancy. Both venlafaxine and its active metabolite possess prolonged half-lives in adults; however, abrupt discontinuation may lead to withdrawal including irritability, jitteriness, lethargy, restlessness, and insomnia. The drug and its metabolite readily cross the placenta, posing additional considerations during pregnancy. Two neonates were admitted to our hospital on 5 and 6 days of life with hypothermia and lethargy among other symptoms of neonatal abstinence syndrome (NAS) requiring an extensive medical workup. Both neonates were exposed to venlafaxine and exclusively fed infant formula since birth. Given that venlafaxine crosses the placenta and into breastmilk, NAS was suspected as a result of the abrupt discontinuation of venlafaxine upon delivery, and the decision was made to introduce mothers' breast milk. Symptoms of NAS, including hypothermia, resolved in both patients. The reported incidence of NAS with venlafaxine alone is limited, likely due to variation in breastfeeding practices among new mothers. Diagnosis of NAS due to venlafaxine requires a high index of suspicion because symptoms are nonspecific and the presentation may be delayed after birth. The effective treatment of NAS using mothers' breast milk illustrates the importance of counseling mothers to provide breast milk as a preventative strategy for withdrawal in their newborns. The cases involving the 2 neonates described in this article emphasize the importance of assessing exposure to medications beyond the immediate newborn period and their possible role in causing unusual symptoms in newborns.