Most of the primary conditions with eosinophilia have now been characterized by clonality in 2008 by the WHO classification, which thereby provide a basis for separation of patients who may benefit a targeted therapy, i.e. by tyrosine kinase inhibition--and who may not. Treatment with interferon-α was introduced some 20 years ago and still has a role in subsets of patients, which is evident from this review of casuistic reports of treatment. However, controlled, randomized, prospective, clinical trials in multi-center studies are needed to clarify dosages, monitoring, prognosis and perhaps combination therapies with interferon-α, i.e. antibodies or other immune suppressants, in the rare patients with primary eosinophilia.