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This review will focus on the diagnostic features of atopic keratoconjunctivitis (AKC), its relationship to atopic dermatitis, the immunopathogenesis, and therapy, and will include strategies used for the management of severe disease unresponsive to conventional therapy.Recent research has demonstrated the importance of various cytokines (IL-33), proteins (thymic stromal lymphopoetin) and effector cells (conjunctival epithelial cells, eosinophils and basophils) in the pathogenesis of chronic ocular inflammation. Current evidence supports the use of tacrolimus and cyclosporin A, topically or systemically, as well tolerated and effective steroid sparing agents.Recalcitrant AKC may be a blinding condition. Understanding the immunopathogenesis of atopic dermatitis and AKC has already influenced therapy and is essential to the development of future immunomodulatory treatments. The successful management of AKC requires the use of topical cromones, antihistamines and calcineurin inhibitors. Severely affected patients also require systemic immunosuppressive therapy. The current challenge is to find more specific topical and systemic immunomodulatory therapies with a better side-effect profile.