Atopic dermatitis is the most common skin disease seen during childhood. Other allergic diseases may accompany atopic dermatitis and increased IgE and peripheral blood eosinophilia are common findings. Patients with atopic dermatitis who do not respond to standard treatment measures should be reassessed for differential diagnosis. Early-onset, treatment resistant severe atopic dermatitis with recurrent infection history apart from the infections occurring due to defective skin integrity are the warning signs for an underlying primary immunodeficiency. Clinicians should always remember that atopic dermatitis may be the first finding of an underlying primer immunodeficiency in patients. The sooner the diagnosis is made, the more likely it will be to avoid complications and morbidity.