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As it appears that we are currently at the cusp of an era in which drugs that are new, re-purposed, or "supplements" will be introduced to the management of celiac disease, we need to reflect on whether the framework is set for celiac disease to be treated increasingly with pharmaceuticals as well as diet. This refers to reflecting on the rigor of current diagnostic practices; the limitations of the current standard of care, which is a gluten-free diet; and that we lack objective markers of disease severity. Investigating these issues will help us to identify gaps in technology and practices that could be critical for selecting patients with a well-defined need for an improved or alternative treatment. Both aspects, circumscribed limitations of the gluten-free diet and diagnostics helping to define celiac disease target groups, together with the guiding requirements by the responsible regulatory authorities, will contribute to defining the subgroups of patients with confirmed celiac disease eligible for distinct pharmacologic strategies. Because many patients with celiac disease are diagnosed in childhood, these aspects need to be differentially discussed for the pediatric setting. In this perspective, we aimed to describe these contextual issues and then looked ahead to the future. What might be the major challenges in celiac disease clinics in the coming years once drugs are an option alongside diet? And what will be the future objectives for researchers who further decipher the mucosal immunology of celiac disease? Speculating on the answers to these questions is as stimulating as it is fascinating to be part of this turning point., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)