A gluten-free diet is the safest treatment for the treatment of patient with celiac disease (CD) and other gluten-related disorders. However, in the last years, gluten-free diet is one of the most popular diet followed by the general population and by patients affected from others clinical conditions, such as non-celiac gluten sensitivity (NCGS), irritable bowel syndrome (IBS), autism, neurological, psychiatric and rheumatologic diseases and for improving sports practice. This review highlights some questions about the appropriateness of following this trend answering to some questions such as how safe are the current gluten-free products, what are the benefits and side effects of gluten-free diet and what are clinical conditions that might benefit from gluten avoidance.