Background. The aim of this study was to quantify behavioral problems in clinically treated children and adolescents with asthma and to examine the association of these problems and quality of life with difficult-to-treat asthma. Methods. Clinical patients with difficult-to-treat asthma (n = 31) and patients with asthma who were not classified as difficult-to-treat asthma (n = 52) completed the Pediatric Asthma Quality of Life Questionnaire [PAQLQ(S)]. Their parents completed the Child Behavior Checklist (CBCL) to assess behavioral problems. Behavioral problem scores were compared to norms of population reference groups and both behavioral problems and quality of life were compared between children and adolescents with and without difficult-to-treat asthma. Results. Especially internalizing behavioral problems such as being withdrawn/depressed and somatic complaints were more severe in the asthmatic groups compared to the healthy reference groups. The behavioral problems 'somatic complaints' and 'thought problems' as well as a lower quality of life were more severe in children and adolescents with difficult-to-treat asthma than in asthma patients who did not fulfill the criteria of difficult-to-treat asthma. Conclusions. Behavioral problems and a lower quality of life are suggested to be more pronounced in clinically treated children and adolescents with difficult-to-treat asthma than in asthma patients who are not classified as difficult-to-treat asthma. With respect to practical implications, our data suggest that health-care professionals should - especially in children and adolescents with difficult-to-treat asthma - assess and, if necessary, treat behavioral problems. © 2011 Informa Healthcare USA, Inc.