Celiac disease (CD) is a chronic autoimmune disorder triggered by the ingestion of gluten in genetically predisposed individuals. It is characterized by immune-mediated damage to the small intestine, leading to a variety of gastrointestinal and extraintestinal symptoms. The disease is strongly associated with the HLA-DQ2 and HLA-DQ8 haplotypes, which play a critical role in its pathogenesis. These genetic markers are present in over 99% of CD patients and are essential for diagnosis, particularly in individuals with atypical or subtle symptoms. The diagnosis of CD relies on a combination of serological tests, histological examination, and genetic testing, with HLA typing offering valuable insights, particularly when other diagnostic methods are inconclusive. This paper reviews the role of HLA-DQ2 and HLA-DQ8 in CD detection, their distribution across different populations, and their clinical implications in diagnosis. It also highlights the limitations of current diagnostic techniques, such as serological testing and biopsies, and discusses the potential benefits of HLA genotyping in screening high-risk groups, including first-degree relatives. Furthermore, the paper explores the integration of nutrigenetic approaches in the management of CD, offering personalized dietary recommendations based on genetic predisposition to prevent disease onset or complications.