Seven to thirteen percent of women are either prescribed or taking (depending on the study) an antidepressant during pregnancy [1]. Although generally low risk, antidepressants have been associated with postnatal adaptation syndrome [2]. Because antidepressants freely cross into the intrauterine environment, it is our aim to summarize the current findings on placental transfer of antidepressants. The antidepressants reviewed are limited to those that are commonly prescribed to the pregnant patient suffering from depression or anxiety. The biological mechanisms regulating placental transport are both complex and multi-determined. Placental anatomy and pharmacokinetics are reviewed along with the latest advances in the understanding of active cellular molecular transport and placental metabolism. In addition, we consider how non-placental and fetal factors contribute to the distribution of drugs across the placenta. The data on placental passage of antidepressants is discussed in the context of the three commonly used research methodologies: animal models, ex vivo perfusion models, and in vivo models. The goal of this review is to inform clinical decision-making by improving understanding of how placental and pharmacokinetic factors relate to the data on antidepressant drug transfer and postnatal adaptation syndrome (PNAS). Incorporating maternal and fetal genetics will be the next step in assisting clinicians to make more informed choices regarding which antidepressants are the least likely to have extensive fetal exposure.