This study compared the health-related quality of life (HRQL) of 236 children with mild or moderate/severe asthma with that of a large representative sample of children in the general community. The study also examined the relationship between the HRQL of children with asthma and their demographic characteristics, asthma severity and family functioning. Children with asthma had a significantly poorer HRQL than other children in the community. Amongst the children with asthma, parents reported that children living in single-parent families had poorer physical health, mental health and social functioning than children in two-parent families. There was a significant relationship between the mental health of children with asthma and family functioning but no significant relationship between their physical health and family functioning. These findings suggest that the domains comprising the HRQL of children with asthma are related to both disease and non-disease factors. A better understanding of these relationships will facilitate the development of new interventions to help children with asthma.