Pharmacologic treatment of depression during pregnancy has become increasingly common, with approximately 6–8% of women taking antidepressants during preg­nancy (Andrade etal. 2016; Huybrechts et al. 2013). Traditionally, the decision about whether to take psychotropic medications during pregnancy has been described as a risk-benet analysis, when it is more correctly framed as a risk-risk analysis. Since there are no randomized placebo-controlled studies on the effects of psychotropic medication and depression (or other psychiatric disorders) on preg­nancy and infant outcomes, conclusions are largely based on case-control or cohort studies. Many of these are observational studies derived from clinical databases and thus are subject to confounding variables. The most troubling of these is that exist­ing studies have not been able to analyze whether adverse outcomes are associated with antenatal psychotropic medications or the condition for which the medications have been prescribed (“confounding by indication”). It is incumbent upon clinicians to help patients sort through alternative options, while understanding the incomplete and uncertain nature of available data.