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Objectives This report focused on four questions: Does screening for subclinical thyroid dysfunction reduce morbidity or mortality? What are the harms of screening for subclinical thyroid dysfunction? Does treatment of patients with subclinical hypothyroidism or subclinical hyperthyroidism detected by screening affect outcomes? What are the harms of treatment of subclinical hypothyroidism and subclinical hyperthyroidism? Data Sources A research librarian searched MEDLINE, the Cochrane Register Database of Systematic Reviews, and the Database of Abstracts of Reviews of Effects from inception to May 2010 for systematic reviews. Additionally, MEDLINE, AGELINE (AARP.org), EMBASE, the Cochrane Central Register of Controlled Trials, CINAHL, and World Health Organization’s Global Health Library from 2002 to May 2010 were searched for new studies. Finally, additional materials were sought by searching for regulatory information, clinical trial registries, conference proceedings, and other sources of gray literature. Review Methods Studies were selected based on predetermined eligibility criteria, with two investigators reviewing abstracts and full articles. English and non-English studies were eligible for inclusion. Randomized controlled trials (RCTs) and observational studies were used to determine the benefits of screening, and RCTs, controlled trials, cohort studies, case-controlled studies, and observational studies were reviewed to determine screening harms and treatment benefits and harms. Two investigators assessed study data and quality. Main Results Three systematic reviews met our inclusion criteria; none found screening or treating subclinical thyroid dysfunction to be beneficial. Since 2002, no studies have directly assessed the benefits or harms of screening. Six good-to fair-quality studies found that treating subclinical hypothyroidism did not improve quality of life, blood pressure, or body mass index (BMI). The findings regarding lipids were inconsistent, with two studies showing a small benefit to treatment and two studies finding no benefit to treatment. Two small poor-quality studies that evaluated the benefits of treating subclinical hyperthyroidism met our inclusion criteria. One study found a small change in the mean daytime systolic blood pressure, while the other found a small increase in BMI with treatment. Treatment harms were neither systematically evaluated nor well described. Conclusions Currently there are no studies that evaluate the benefits and harms of screening for subclinical thyroid dysfunction in the primary care setting. Studies of treatment tend to be small and of short duration, and they have failed to demonstrate improvement in quality of life, blood pressure, and weight. The data concerning lipids is inconsistent, but at best, treatment might cause a modest (about 5-percent) improvement in lipid measurements. The lack of any formal data on the harms of treatment makes it difficult to balance the benefits against the harms of treatment. Further research is needed to determine if screening and/or treating subclinical thyroid dysfunction is beneficial or harmful.