Insulin allergy was not uncommon in the past, but has lowered with the introduction of human recombinant insulin. Human recombinant insulin allergy is a rare condition, now reported in less than 1% of treated patients. However, it is a serious condition that requires an immediate allergological work-up. In this study, we describe 4 cases of IgE-mediated reaction to human recombinant insulin, emphasizing some practical aspects in diagnosis and treatment.