| The goal of this Review is to discuss the clinical approach to patients who do not respond to treatment for eosinophilic oesophagitis (EoE). Refractory EoE is challenging to manage as there are limited data to guide decision-making. In this Review, refractory EoE is defined as persistent eosinophilia in the setting of incomplete resolution of the primary presenting symptoms and incomplete resolution of endoscopic findings following a PPI trial, and after treatment with either topical steroids or dietary elimination. However, this definition is controversial. This Review will examine these controversies, explore how frequently non-response is observed, and highlight potential explanations and predictors of non-response. Non-response is common and affects a large proportion of patients with EoE. It is important to systematically assess multiple possible causes of non-response, as well as consider treatment complications and an incorrect diagnosis of EoE. If non-response is confirmed, second-line treatments are required. Although the overall response rate for second-line therapy is disappointing, with only half of patients eventually responding, there are several promising agents that are currently under investigation, and the future is bright for new treatment modalities for refractory EoE.