Depression affects approximately 10% of pregnant women, and antenatal antidepressant use has been increasing over the last two decades. The decision about whether to take psychotropic medications during pregnancy requires a risk-risk analysis, weighing the impact of untreated maternal depression against the risks of antidepressant exposure in utero. The treating clinician must sort through the most current data with the patient, recognizing that most existing studies have not been able to analyze whether small increases in adverse outcomes are associated with antenatal psychotropic medications or the condition for which the medications have been prescribed, a situation known as “confounding by indication.” While decisions about medication use during pregnancy are individualized, if a woman is experiencing severe depression and is functionally impaired, or has a history of psychosis, suicide attempts, chronic depression, or relapses following medication discontinuation, treatment with antidepressants is advisable. Serotonin reuptake inhibitors (SSRIs) are the best studied antidepressants and therefore are generally preferred. However, if a woman has responded well to a particular medication in the past, that medication is often the best starting point for treatment. A general principle of reproductive psychiatry is to treat perinatal patients with the fewest number of medications at the lowest effective dose. Caution should be exercised not to undertreat pregnant women, creating a situation of dual exposure to both a sub-therapeutic dose of medication and an only partially treated disease state. For postpartum depression, SSRIs are again the best studied medications and are considered first-line in medication-naïve patients. For women who were treated during pregnancy, treatment should continue with previously effective medications. Most antidepressants are compatible with breastfeeding; however, attention should be paid to the mental health impact of sleep deprivation often associated with nursing and pumping breast milk.