Autism spectrum disorders (ASDs) are characterized by impairments in social interaction, communication and behavioral functioning that can affect the health-related quality-of-life outcomes of the affected child and the family. ASDs have increased in prevalence, leading to a demand for improved understanding of the comparative effectiveness of different pharmacologic, behavioral, medical and alternative treatments for children as well as systems for providing services. This review describes outcome instruments that can be used for clinical, health services and cost-effectiveness applications. There is a pressing need to identify the most appropriate instruments for measuring health-related quality-of-life outcomes in this population. Studies evaluating the cost-effectiveness of interventions or treatments for children with ASDs using the cost per quality-adjusted life year metric are lacking. Researchers have the potential to contribute greatly to the field of autism by quantifying outcomes that can inform optimal treatment strategies.