Hyper-IgE syndromes (HIES) are a heterogeneous group of inborn errors of immunity. The underlying cause of HIES is dominant mutations in various signal transduction and activators of transcription genes with the most common type is mutation in the STAT3 gene located on chromosome 17 followed by mutation in DOCK8 gene. The disease is very rare with prevalence less than 1 per million population. Elevated IgE level is the cardinal feature of the disease. Clinical features include recurrent eczema, frequent bacterial infections, and mucocutaneous candidiasis. Treatment is usually symptomatic including prophylactic antibiotics. Bone marrow transplantation & stem cell therapy can be used for recalcitrant cases. Recently, biologics have emerged as an additional option for treating HIES with treatment refractory atopic dermatitis. Dupilumab, a human monoclonal antibody that blocks the shared receptor subunit of IL-4 and IL-13, mitigates the signs and symptoms of atopic dermatitis. Few case reports have demonstrated the substantial improvements of atopic dermatitis following the injection of dupilumab in HIES. Here, we present two cases of different age groups whom atopic dermatitis was treated successfully using dupilumab, an IL-4 / IL-13 antagonist.