Persistent pulmonary hypertension of the newborn (PPHN) is a rare but potentially life-threatening neonatal condition. Several authors have suggested that late pregnancy exposure to selective serotonin reuptake inhibitors (SSRIs) may increase the risk of PPHN. This association has been investigated in seven published studies that have shown mixed findings based on diverse methods. Several methodological limitations may account for the diversity of findings, which include, in some studies, a lack of control for well established risk factors for PPHN. The methodological improvement in the most recent study tentatively suggests that infants prenatally exposed to SSRIs are approximately twice as likely to suffer PPHN. Further research on the biological mechanisms involved is required. Clinicians should consider late pregnancy exposure to SSRIs as one of several possible risks for PPHN, which has implications for both prescribing SSRIs to pregnant women and for neonatal care of SSRI-exposed infants.