Atopic dermatitis is the most common skin disorder diagnosed in early childhood. Some children do not experience a relief of symptoms as they get older, and severe atopic dermatitis may develop, with manifestations including widespread skin lesions and unremitting itching. The disease is both physically and emotionally disabling, and significantly compromises the patient’s quality of life. Indications to intensify therapy include resistance to topical treatment and multidrug resistance. However, in many cases non-adherence to the treatment regimen, including inadequate skin care techniques, contribute to the development of severe or refractory atopic dermatitis. Persistent eczematous lesions may be a result of exacerbating environmental factors, secondary infection, and hypersensitivity reactions to topical treatments or other allergens. Wet-wrap treatment with topical corticosteroids, narrow-band UVB phototherapy and systemic immunosuppressive drugs, such as cyclosporine A, methotrexate, mycophenolate mofetil and azathioprine, are recommended for the treatment of severe atopic dermatitis in children. However, there are no evidence-based guidelines for using these agents. Systemic corticosteroids should be avoided, but they can be used for a short period of time for the immediate relief of acute flares before introducing other therapies. Patients need a holistic approach including education and modern biopsychosocial techniques. Paediatric studies are currently under way to test the safety and tolerability of dupilumab which was approved by the US Food and Drug Administration in 2017 for the treatment of adults with moderate-to-severe atopic dermatitis.