Prerequisites for successful treatment of severe asthma in children and adolescents with biological drugs are: 1) systematic assessment, excluding and treating other causes of lack of asthma control, 2) immunological phenotyping of the patient, and 3) choice of biological drug targeting the specific disease mechanism. Anti-immunoglobulin (Ig) E and anti-interleukin (IL)-5 have a clinically relevant effect reducing exacerbation rate, but there is still a need for studies in children and adolescents being treated with anti-IgE and anti-IL-5 as well as newer biological drugs, which affect lung function, asthma control and quality of life.