Increasing prevalence, protean clinical manifestations, and lack of pharmacological therapy make celiac disease (CD) a complex and highly relevant illness in gastroenterology. This chronic inflammatory disorder of the small intestine is caused by the ingestion of gluten containing cereals in genetically susceptible individuals, leading to a variety of gastrointestinal (GI) and non-GI manifestations. Awareness among physicians is growing due to accessible and highly accurate diagnostic and screening methods. Recent evidence suggests a possible rising incidence of CD. Environmental factors such as early life gluten exposure, intestinal infections, short duration of breast-feeding, and changes in intestinal microbiota have been proposed to have a role in CD pathogenesis. Thus, prevention approaches to diminish the rising prevalence of CD are currently being evaluated. Still, the cornerstone treatment of CD remains a strict gluten-free diet. This nutritional regime is demanding, and non-adherence is common because of social isolation, financial issues, or restriction of food diversity. Allowing patients to occasionally consume small amounts of gluten would greatly improve their quality of life. Owing to recent advances in the understanding of the pathogenesis of CD, different targets have been identified and have motivated the development of several experimental therapeutic strategies. The main goal of this review is to discuss the mechanisms that can be exploited therapeutically to prevent or delay CD, disease associations and its complications. Current treatments for complications of CD, including refractory CD and malignancy, are beyond the scope of this review.