Objective We compared the levels of academic, physical, and social functioning of children and adolescents with chronic physical diseases with those of healthy peers or test norms. Methods A random effects meta-analysis was computed to integrate the results of 954 studies. Results Impairments of physical functioning (g = 0.82 standard deviation units) were stronger than impairments of academic (g = 0.53) and social functioning (g = 0.43). Children with cerebral palsy and spina bifida showed the largest levels of functional impairments. The levels of functional impairments also varied by year of publication, source of information, ethnicity, country, and sociodemographic equivalence of the compared groups. Conclusions More efforts are needed to develop and implement measures for the prevention of impaired functioning of children and adolescents with chronic physical illness and for the reduction of already existing impairments of their functioning.