Despite dramatic advances in our understanding of the pathogenesis and course of disease in the relatively short timeframe since the discovery and first description of eosinophilic esophagitis (EoE) less than three decades ago, many open questions remain to be elucidated. For instance, we will need to better characterize atypical clinical presentations of EoE and other forms of esophageal inflammatory conditions with often similar clinical presentations, nut fulfilling current diagnostic criteria for EoE and to determine their significance and interrelationship with genuine EoE. In addition, the interrelationship of EoE with other immune-mediated diseases remains to be clarified. Hopefully, a closer look at the role of environmental factors and their interaction with genetic susceptibility often in context of atopic predisposition may enable identifying the candidate substances/agents/allergens and potentially earlier (childhood) events to trigger the condition. It appears plausible to assume that in the end-comparable to current concepts in other immune-mediated chronic diseases, such as for instance inflammatory bowel disease or asthma bronchiale-we will not be rewarded with the identification of a "one-and-only" underlying pathogenetic trigger factor, with causal responsibility for the disease in each and every EoE patient. Rather, the relative contribution and importance of intrinsic susceptibility, i.e., patient-driven factors (genetics, aberrant immune response) and external trigger factors, such as food (or aero-) allergens as well as early childhood events (e.g., infection and exposure to antibiotics and other drugs) may substantially differ among given individuals with EoE. Accordingly, selection and treatment duration of medical therapy, success rates and extent of required restriction in dietary treatment, and the need for mechanical treatment to address strictures and stenosis require an individualized approach, tailored to each patient. With the advances of emerging treatment options, the importance of such an individualized and patient-centered assessment will increase even further.