Eosinophilic esophagitis (EoE) is an allergen-mediated condition characterized by symptoms of esophageal dysfunction and histologic evidence of intense eosinophilic inflammation involving the esophagus in the absence of overlapping conditions such as gastroesophageal reflux disease. Since the initial description as a distinct entity approximately 2 decades ago, there has been a remarkable increase in the recognition of this clinicopathologic entity. The current approach to diagnose and monitor EoE requires repeated esophagogastroduodenoscopies, with associated sedation/anesthesia, to visualize mucosal abnormalities, and to obtain multiple biopsy specimens for histologic assessment and to evaluate treatment response. Frequent esophagogastroduodenoscopies with multiple biopsies can increase the risk of procedural complications, place significant financial burden on families, and escalate health care costs. In addition, this burdensome approach may contribute toward delayed diagnosis and suboptimal monitoring, thereby increasing the likelihood of complications such as esophageal narrowing and stricture formation, which may require escalation of care including endoscopic interventions. Clinical progression and complications associated with EoE can be attenuated through early identification and optimal management. Therefore, developing reliable, safe, less-cumbersome, and cost-effective modalities for early diagnosis and effective monitoring of EoE is an area of active research. These efforts have been substantially supported by the development of new biomaterials, analytic methodologies, and the application of novel concepts. Herein, we summarize modalities that have shown promise to advance the diagnosis and monitoring of EoE and could improve the care of affected individuals and advance the field.