PurposeThis review aims to outline a systematic approach for the assessment of quality of life in children and adolescents with CHD and to cite its main determinants.MethodsA systematic critical literature search in PubMed, Scopus, and Cinahl databases resulted in 954 papers published after 2000. After the quality assessment, 32 original articles met the inclusion criteria.ResultsMethodological quality of the included studies varied greatly, showing a moderate quality. Impaired quality of life was associated with more severe cardiac lesions. Children with CHD, after cardiac surgery, reported diminished quality of life concerning physical, psycho-social, emotional, and school functioning. The majority of clinical studies showed significant differences among children and their parents’ responses regarding their quality of life, with a tendency of children to report greater quality of life scores than their parents. According to our analysis, concerning children with CHD, the most cited determinants of their quality of life were as follows: (a) parental support; (b) lower socio-economic status; (c) limitations due to physical impairment; (d) sense of coherence; as well as (e) the level of child’s everyday anxiety and depression. These findings suggest that differences in quality of life issues may exist across lesion severities.ConclusionQuality of life in children with CHD should be assessed according to age; severity; therapeutic approach; acceptance of the disease; and personality features. Effective management and early recognition of significant impairments in quality of life could impact clinical outcomes in children with CHD.