IMPORTANCE: Depression is a source of substantial burden for individuals and their families, including women during the pregnant and postpartum period. OBJECTIVE: To systematically review the benefits and harms of depression screening and treatment, and accuracy of selected screening instruments, for pregnant and postpartum women. Evidence for depression screening in adults in general is available in the full report. DATA SOURCES: MEDLINE, PubMed, PsycINFO, and the Cochrane Collaboration Registry of Controlled Trials through January 20, 2015; references; and government websites. STUDY SELECTION: English-language trials of benefits and harms of depression screening, depression treatment in pregnant and postpartum women with screen-detected depression, and diagnostic accuracy studies of depression screening instruments in pregnant and postpartum women. DATA EXTRACTION AND SYNTHESIS: Two investigators independently reviewed abstracts and full-text articles and extracted data from fair- and good-quality studies. Random-effects meta-analysis was used to estimate the benefit of cognitive behavioral therapy (CBT) in pregnant and postpartum women. MAIN OUTCOMES AND MEASURES: Depression remission, prevalence, symptoms, and related measures of depression recovery or response; sensitivity and specificity of selected screening measures to detect depression; and serious adverse effects of antidepressant treatment. RESULTS: Among pregnant and postpartum women 18 years and older, 6 trials (n = 11,869) showed 18% to 59% relative reductions with screening programs, or 2.1% to 9.1% absolute reductions, in the risk of depression at follow-up (3-5 months) after participation in programs involving depression screening, with or without additional treatment components, compared with usual care. Based on 23 studies (n = 5398), a cutoff of 13 on the English-language Edinburgh Postnatal Depression Scale demonstrated sensitivity ranging from 0.67 (95% CI, 0.18-0.96) to 1.00 (95% CI, 0.67-1.00) and specificity consistently 0.87 or higher. Data were sparse for Patient Health Questionnaire instruments. Pooled results for the benefit of CBT for pregnant and postpartum women with screen-detected depression showed an increase in the likelihood of remission (pooled relative risk, 1.34 [95% CI, 1.19-1.50]; No. of studies [K] = 10, I2 = 7.9%) compared with usual care, with absolute increases ranging from 6.2% to 34.6%. Observational evidence showed that second-generation antidepressant use during pregnancy may be associated with small increases in the risks of potentially serious harms. CONCLUSIONS AND RELEVANCE: Direct and indirect evidence suggested that screening pregnant and postpartum women for depression may reduce depressive symptoms in women with depression and reduce the prevalence of depression in a given population. Evidence for pregnant women was sparser but was consistent with the evidence for postpartum women regarding the benefits of screening, the benefits of treatment, and screening instrument accuracy.