Depression is a potentially life-threatening condition. The incidence of depression during pregnancy and the postpartum period is estimated to be anywhere from 5.5 to 33.1 percent, and the American Academy of Pediatrics estimates that more than 400,000 infants are born each year to mothers who are depressed. Depression during pregnancy is known to be associated with harmful prenatal health consequences, such as poor nutrition, poor prenatal medical care, risk of suicide, and harmful health behaviors (e.g., smoking and alcohol or other substance misuse). These circumstances compromise the health of both the woman and her fetus. Although causation has not been proven, several obstetric complications have been reported with untreated prenatal depression, including preeclampsia, preterm delivery, low birth weight, miscarriage, small-for-gestational-age babies, low Apgar scores, and neonatal complications. These complications may be more common among women with lower socioeconomic status. In addition to being debilitating for the mother, postpartum depression affects maternal-infant interactions and some measures of infant development. In extreme cases, postpartum depression may increase the risk of infant mortality through neglect, abuse, or homicide. It also negatively affects interactions within other members of the family unit and is associated with intimate partner violence. Clinicians can use interventions such as pharmacological treatments, nonpharmacological treatments, and watchful waiting for patients with depression, both during pregnancy and in the postpartum period; they may also elect not to provide any intervention at all. Antidepressant medications have been shown to be effective at reducing the symptoms of depression in nonpregnant adults. In general, medications that are effective in treating conditions outside of pregnancy are often presumed to remain effective in pregnancy, but the developing fetus and changes in maternal physiology raise questions about safety and dosing of various agents. However, evidence on how the risk of one antidepressant compares with that of another when taken during pregnancy is not well understood. Antidepressant medications are used to treat a variety of other indications, including anxiety disorders such as generalized anxiety disorder, panic attacks, obsessive compulsive disorder, depressed phase of bipolar disorder, and neuropathic pain. A wide array of nonpharmacological interventions can be used to treat depression, including various psychotherapies, electroconvulsive therapy, repetitive transcranial magnetic stimulation, and acupuncture. Some of these may be used during pregnancy, whereas others may be reserved for use in the postpartum period (e.g., electroconvulsive therapy). Decisionmaking surrounding treatment of depression in pregnancy is complex because the harms of treatments must be balanced against the potential harms to mother and fetus of untreated depression. The objective of this systematic review was to evaluate the benefits and harms of various pharmacological treatment options for depression during pregnancy and the postpartum period compared with each other, with nonpharmacological treatments, and with usual care or no treatment.