Health-related quality of life (HRQOL) assessment in children and adolescents with chronic health conditions is increasingly considered as a relevant topic. The aim of the EU-funded DISABKIDS project is to develop, test, and implement European instruments for the assessment of HRQOL of children and adolescents with disabilities and their families. The current paper describes the development and pilot testing of a chronic generic HRQOL measure. Using literature searches, expert consulting and focus groups with children/adolescents and their families, items of the instruments were developed and translated into the respective languages. A pilot test with 360 children and adolescents was conducted. Children and adolescents (8-12, 13-16 years) with different chronic health conditions (asthma, epilepsy, diabetes, arthritis, atopic dermatitis, cerebral palsy, and cystic fibrosis) as well as their families were included. Data were analysed according to predefined psychometric and content criteria. Psychometric analyses resulted in a 56-item chronic generic HRQOL questionnaire with six domains ('Medication', 'Physical', 'Emotion', 'Independence', 'Social Inclusion', 'Social Exclusion') with acceptable internal consistency.