Background: Asthma is the most frequent chronic respiratory disease in childhood and adolescence. While good control can be achieved in the majority of patients with guideline-conform treatment, a relevant subgroup suffer from asthma that is difficult to treat with frequent exacerbations and impaired quality of life. Objective: These guidelines aim to clearly define severe and difficult to treat asthma in childhood and adolescence, to promote a structured diagnostic and treatment approach and to provide practical, evidence-based recommendations for the management, including the use of biologicals. Methods: The guidelines were developed under the coordination of the Society for Pediatric Pulmonology (GPP) following the Association of Scientific Medical Societies in Germany (AWMF) procedures. A structured consensus process involving experts from pediatric pulmonology, allergology and general pediatrics was conducted. A systematic review of the literature on national and international recommendations was carried out. Results: Key elements include a multistage diagnostic approach to distinguish difficult to treat from genuine severe asthma. Criteria for treatment adherence, documentation of comorbidities and phenotype-specific selection of biologicals are presented. Further topics are monitoring, rehabilitation, transition and future forms of treatment. Recommendations on the application of existing and novel monoclonal antibodies are based on the current evidence. Conclusion: Children and adolescents with severe asthma require early referral to specialized centers and a structured, interdisciplinary approach. An early phenotype-based treatment with biologicals, comprehensive register data and patient-oriented treatment pathways are necessary in order to improve the prognosis in this group of patients and to generate real-world evidence.