Importance Depression, suicidal ideation, and self-harm behaviors in youth are associated with functional impairment and suicide. Objective To review the evidence on screening for depression or suicide risk in children and adolescents to inform the US Preventive Services Task Force (USPSTF). Data Sources PubMed, Cochrane Library, PsycINFO, CINAHL, and trial registries through July 19, 2021; references, experts, and surveillance through June 1, 2022. Study Selection English-language, randomized clinical trials (RCTs) of screening for depression or suicide risk; diagnostic test accuracy studies; RCTs of psychotherapy and first-line pharmacotherapy; RCTs, observational studies, and systematic reviews reporting harms. Data Extraction and Synthesis Two reviewers assessed titles/abstracts, full-text articles, and study quality and extracted data; when at least 3 similar studies were available, meta-analyses were conducted. Main Outcomes and Measures Test accuracy, symptoms, response, remission, loss of diagnosis, mortality, functioning, suicide-related events, and adverse events. Results Twenty-one studies (N = 5433) were included for depression and 19 studies (N = 6290) for suicide risk. For depression, no studies reported on the direct effects of screening on health outcomes, and 7 studies (n = 3281) reported sensitivity of screening instruments ranging from 0.59 to 0.94 and specificity from 0.38 to 0.96. Depression treatment with psychotherapy was associated with improved symptoms (Beck Depression Inventory pooled standardized mean difference, −0.58 [95% CI, −0.83 to −0.34]; n = 471; 4 studies; and Hamilton Depression Scale pooled mean difference, −2.25 [95% CI, −4.09 to −0.41]; n = 262; 3 studies) clinical response (3 studies with statistically significant results using varying thresholds), and loss of diagnosis (relative risk, 1.73 [95% CI, 1.00 to 3.00; n = 395; 4 studies). Pharmacotherapy was associated with improvement on symptoms (Children’s Depression Rating Scale–Revised mean difference, −3.76 [95% CI, −5.95 to −1.57; n = 793; 3 studies), remission (relative risk, 1.20 [95% CI, 1.00 to 1.45]; n = 793; 3 studies) and functioning (Children’s Global Assessment Scale pooled mean difference, 2.60 (95% CI, 0.78 to 4.42; n = 793; 3 studies). Other outcomes were not statistically significantly different. Differences in suicide-related outcomes and adverse events for pharmacotherapy when compared with placebo were not statistically significant. For suicide risk, no studies reported on the direct benefits of screening on health outcomes, and 2 RCTs (n = 2675) reported no harms of screening. One study (n = 581) reported on sensitivity of screening, ranging from 0.87 to 0.91; specificity was 0.60. Sixteen RCTs (n = 3034) reported on suicide risk interventions. Interventions were associated with lower scores for the Beck Hopelessness Scale (pooled mean difference, −2.35 [95% CI, −4.06 to −0.65]; n = 644; 4 RCTs). Findings for other suicide-related outcomes were mixed or not statistically significantly different. Conclusion and Relevance Indirect evidence suggested that some screening instruments were reasonably accurate for detecting depression. Psychotherapy and pharmacotherapy were associated with some benefits and no statistically significant harms for depression, but the evidence was limited for suicide risk screening instruments and interventions.