OBJECTIVES: Epilepsy represents the most prevalent and serious neurological condition affecting children in their developing years. Epilepsy has a significant impact on the health-related quality of life (HRQoL) of children and their families. In the last decade, significant advances have been made to measure HRQoL in children and adolescents with epilepsy; resulting in the development of several HRQoL instruments. The aim of this study is to provide a comprehensive review of HRQoL instruments used in children and adolescents with epilepsy. METHODS: A literature review was conducted from January 1990 - December 2006 using the following databases: Medline, PsycINFO, and CINAHL using a combination of keywords like ‘quality of life', ‘epilepsy', ‘seizures', ‘children', ‘adolescents' and ‘instruments'. The instruments included in the review were evaluated based on the number of items and domains, scaling methods, and psychometric properties. RESULTS: The literature search yielded 13 instruments including 4 generic, 7 epilepsy-specific, and 2 domain-specific instruments. The most widely used generic, epilepsy-specific, and domain-specific instruments were Impact of Childhood Illness Scale, Quality of Life in Childhood Epilepsy Questionnaire, and Hague Restriction in Epilepsy Scale, respectively. The HRQoL instruments varied widely in the age range (2-18 years), length of the instruments (10-125 items), scaling methods, respondents (child or the parent as proxy) and psychometric attributes such as reliability, validity, and responsiveness. Most of the instruments reviewed exhibited satisfactory internal consistency with values ranging from 0.7 to 0.9. Also, most instruments reported test-retest reliability and validity measures like construct, content and criterion validity. CONCLUSION: The comprehensive description of all the HRQoL instruments used in children and adolescents with epilepsy will help researchers and clinicians select the most appropriate instrument. It is hoped that complete understanding of the impact of epilepsy on HRQoL can help in the development of appropriate and effective interventions.