ABSTRACT: BACKGROUND:An estimated 12.8% of children and adolescents experience chronic health conditions that lead to poor quality of life, adjustment and coping issues, and concurrent mental health problems. Digital health deployment of psychosocial interventions to support youth with chronic illness has become increasingly popular with the advent of the technological advances in the digital age. OBJECTIVE:Our objectives were to systematically review published efficacy studies of eHealth and mHealth (mobile health) psychosocial interventions for youths with chronic illnesses and review intervention theory and treatment components. METHODS:PubMed, Embase, Web of Science, PsycInfo, and Cochrane Database of Systematic Reviews were searched for studies published from 2008 to 2019 of eHealth and mHealth psychosocial interventions designed for children and adolescents with chronic illnesses in which efficacy outcomes were reported. We excluded studies of interventions for caregivers, healthy youth, disease and medication management, and telehealth interventions that function solely as a platform to connect patients to providers via phone, text, or videoconference. RESULTS:We screened 2551 articles and 133 relevant full-text articles. Sixteen efficacy studies with psychosocial and health outcomes representing 12 unique interventions met the inclusion criteria. Of the included studies, 12 were randomized controlled trials and 4 were prospective cohort studies with no comparison group. Most interventions were based in cognitive behavioral theory and designed as eHealth interventions; only 2 were designed as mHealth interventions. All but 2 interventions provided access to support staff via text, phone, email, or discussion forums. The significant heterogeneity in intervention content, intervention structure, medical diagnoses, and outcomes precluded meta-analysis. For example, measurement time points ranged from immediately postcompletion of the mHealth program to 18 months later, and we identified 39 unique outcomes of interest. The majority of included studies (11/16, 69%) reported significant changes in measured health and/or psychosocial posttreatment outcomes, with small to large effect sizes. CONCLUSIONS:Although the available literature on the efficacy of eHealth and mHealth psychosocial interventions for youth with chronic illnesses is limited, preliminary research suggests some evidence of positive treatment responses. Future studies should continue to evaluate whether digital health platforms may be a viable alternative model of delivery to traditional face-to-face approaches.