An iron hypersensitivity reaction can develop during infusion. Here we present four cases of Rapid Drug Desensitization (RDD) as an option for the treatment of these patients. Urticaria appeared in the second hour of an IV iron sucrose infusion (ISI) performed 8 years previously in case 1 and drug provocation with IV ferric carboxymaltose was performed, but urticaria developed on the arm where the drug was administered immediately after infusing 60 cc. Case 2 developed tongue swelling and shortness of breath within minutes of the IV ISI. Case 3 developed shortness of breath within three minutes after the first dose of IV ISI. Case 4 with iron deficiency anemia reported swelling in the throat, lips and shortness of breath after taking an unknown oral iron therapy. On the 14th day of oral ferrous sulfate therapy, the patient presented with pruritus and skin eruptions occurring 2 hours after drug ingestion. Fifteen RDDs were successfully performed in these cases.