INTRODUCTION: Celiac disease is one of the most common chronic immune-mediated gastrointestinal conditions, characterized by the presence of disease-specific serum antibodies against self-antigen transglutaminase 2. Even though modern serological assays can identify most untreated celiac disease patients and are also increasingly being used to establish a diagnosis, several challenges are associated with the tests, including a lack of standardization, the variable sensitivity and specificity of commercial assays, and inadequate sensitivity for monitoring adherence to a gluten-free diet. AREAS COVERED: This narrative review outlines the current use of serological tests in case-finding and screening, as well as in the follow-up of dietary treatment. Additionally, the possible challenges and pitfalls of serological tests, along with future directions, are addressed. EXPERT OPINION: The excellent accuracy of modern autoantibody tests, especially for greatly elevated levels of transglutaminase 2 antibodies and positive endomysial antibodies, enables using serological testing in establishing a diagnosis. However, better international standardization of the assays is required, the necessity of endomysial antibody testing needs to be further scrutinized, and additional research is needed to improve noninvasive tools for follow-up and to further expand the no-biopsy criteria for celiac disease.