The purpose of this paper is to highlight important considerations in the measurement of health-related quality of life (HR-QOL) in paediatric populations. Considerations specific to the evaluation of HR-QOL in children include children's understanding of the questions being asked, their understanding of their own disease, using parents as proxies, time perception problems and simply the fact that children are continually changing. We provide a review of the currently available literature regarding paediatric HR-QOL assessments to examine the different instruments and approaches taken to assess HR-QOL in paediatrics. Asthma-specific measures are discussed as examples of condition-specific HR-QOL instruments because of the considerable amount of methodological and developmental work that has been conducted in this disease. Our search strategy revealed 15 main generic and 5 main asthma-specific instruments that met our criteria for inclusion. The main points high-lighted for each instrument are the description of domains, respondent (i.e. the child, parent or clinician), age group, number of items, format of instrument (usually self-administered or by interview), original country and language, and the existence of translations. For the various studies in which the different instruments are used, the issues of patient population tested, sample size, reliability and validity are addressed. Although this paper does not attempt to be an exhaustive study of paediatric HR-QOL instruments, we provide an overview of the main generic and asthma-specific instruments, as well as an examination of the different methods used in assessing paediatric HR-QOL. Many challenges exist in the measurement of HR-QOL in paediatric patients. With increased attention to the considerations high-lighted, the field will continue to grow, and the usefulness and application of HR-QOL measures in paediatric patients is likely to improve.