Celiac disease (CD) is an immune-mediated disorder induced by the ingestion of gluten in genetically susceptible individuals. The enzyme tissue transglutaminase (protein-glutamine gamma-glutamyltransferase 2; tTG) plays an important role in the pathogenesis of the disease and antibodies against tTG are used as serological markers for the diagnosis of CD. Discovery of tTG as the autoantigen for endomysial antibodies changed the diagnostic approach to patients with suspected CD and, importantly, made screening for CD more accurate and easier to perform. Studies in pediatric populations confirmed the high sensitivity and specificity of immunoglobulin A (IgA) tTG antibodies in the diagnosis of CD. The aim of this review is to summarize the data on the role of tTG in the pathogenesis of CD and to present current evidence on the accuracy of IgA tTG, IgG tTG and IgA tTG point-of-care tests in the diagnosis of CD in children. This review shows why IgA tTG antibodies replaced endomysial antibodies as the preferred serological marker due to the ease of their use, their high sensitivity and specificity, and the high correlation between high titers and intestinal mucosal lesions.