The use of imatinib mesylate (Gleevec), a selective tyrosine kinase inhibitor, has become the new gold standard for the treatment of chronic myeloid leukemia. Unfortunately, the medication has been commonly associated with mild to severe cutaneous reactions, which has limited its use for some patients. We describe a case of a successful progressive challenge of a patient with a drug-induced exanthem from imatinib mesylate and a review of the literature.