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This thesis focuses on problematic severe asthma in children and its treatment from a biopsychosocial perspective. Asthma is a chronic inflammatory disease of the airways. In children with problematic severe asthma, asthma is not under control despite optimal medical treatment. Asthma control is the main goal of asthma treatment in these children. This study is guided by a biopsychosocial model, assuming that both disease activity and psychosocial variables influence asthma control and quality of life. In the first part of the thesis, children’s behavioral problems and parenting stress are investigated in relation to asthma control and quality of life in children with problematic severe asthma. In the second part, the effects of multidisciplinary treatment on a broad set of biopsychosocial outcome variables are evaluated. This thesis stimulates multilevel investigations promoting understanding and treatment of the complex biopsychosocial phenomena of problematic severe asthma. This will ultimately reduce the burden, morbidity, and mortality of problematic severe asthma in children.