CONTEXT: Epilepsy is a common and severe neurologic disease associated with increased mortality, seizure-related injury, and adverse psychological and quality-of-life outcomes. OBJECTIVE: To describe the perspectives of children and adolescents with epilepsy. DATA SOURCES: Medline, Embase, PsycINFO, and CINAHL from inception to August 2015. STUDY SELECTION: Qualitative studies on children's experiences of epilepsy. DATA EXTRACTION: Results from primary studies. We used thematic synthesis to analyze the findings. RESULTS: Forty-three articles involving 951 participants aged 3 to 21 years across 21 countries were included. We identified 6 themes: loss of bodily control (being overtaken, susceptibility to physical harm, fragility of the brain, alertness to mortality, incapacitating fatigue), loss of privacy (declarative disease, humiliating involuntary function, unwanted special attention, social embarrassment of medicine-taking), inescapable inferiority and discrimination (vulnerability to prejudice, inability to achieve academically, consciousness of abnormality, parental shame, limiting social freedom), therapeutic burden and futility (unattainable closure, financial burden, overwhelming life disruption, exhaustion from trialing therapies, insurmountable side effects, awaiting a fabled remission), navigating health care (empowerment through information, valuing empathetic and responsive care, unexpected necessity of transition, fragmented and inconsistent care), and recontextualizing to regain normality (distinguishing disease from identity, taking ownership, gaining perspective and maturity, social and spiritual connectedness). LIMITATIONS: Non-English articles were excluded. CONCLUSIONS: Children with epilepsy experience vulnerability, disempowerment, and discrimination. Repeated treatment failure can raise doubt about the attainment of remission. Addressing stigma, future independence, and fear of death may improve the overall well-being of children with epilepsy.