Eosinophilic Esophagitis (EoE) and Crohn's Disease (CD) occurring simultaneously is rare. Our literature search revealed only two documented cases of co-existing EoE and CD, with very limited evidence supporting an association. We present two additional cases to demonstrate these distinct immunemediated diseases can occur together, and propose a unique hypothesis about their immunopathogenic relationship. Case 1: A 27 year old Caucasian female with a 4-year history of CD, whose biologic therapy had been held during pregnancy, presented to our hospital with an abdominal abscess and obstruction. After discharge, her biologic therapy was resumed. Two months later, she had improvement in her CD symptoms but reported new symptoms of solid food dysphagia. EGD revealed changes compatible with EoE. After an 8-week proton pump inhibitor trial, repeat esophageal biopsies showed persistent eosinophilia consistent with a diagnosis of EoE. Case 2: A 30 year old Caucasian male with a history of EoE well controlled on topical budesonide presented to our clinic for a second opinion regarding his 5-year history of fistulizing CD on methotrexate. EGD and colonoscopy confirmed quiescent EoE but active Crohn's ileitis. History was remarkable for several failed CD therapies including immunomodulators and biologics, over which time his EoE remained well controlled. He was subsequently placed on vedolizumab for CD, and topical budesonide was continued for EoE. While it is accepted that CD and EoE are driven primarily by Th1 and Th2-mediated immune responses, respectively, much of the pathophysiology of these two conditions is not yet fully understood. These responses are fostered by differing and often competing cytokine profiles, and it is therefore conceivable that a Th1-mediated condition could help quell a Th2-mediated condition, and vice versa. This is supported by recent advances via epigenetics studies in patients with EoE and inflammatory bowel disease. Our cases present two young, Caucasian patients with co-existent severe CD and EoE. In each case, one of the conditions is quiescent while the other is exacerbated. Patient 1, developed symptoms leading to the diagnosis of EoE only after her CD went into remission with aggressive biologic therapy. Patient 2 manifested treatment-refractory CD when his EoE was well controlled. Our clinical observation questions whether treating one condition can worsen the other as the immune response shifts between Th1 and Th2, or, possibly, whether EoE could be a marker for aggressive CD. As evidenced by recent epigenetics studies, the answers to these questions are undoubtedly complex. Until further advancements, it is important to recognize the potential interplay of diseases such as EoE and CD when managing these complex cases.