Human immunodeficiency virus (HIV) affects millions of people globally. The associated stigma remains a challenge for individuals living with HIV and children and adolescents face the additional challenge of withstanding the peer, pubertal and identity challenges associated with growing up. The current systematic review aimed to define and explore the major stigma-related challenges of children and adolescents from their own perspectives. A secondary aim was to identify any challenges distinct to childhood and adolescence. Studies included individuals aged 3 to 18 years who were aware of their status. Fifteen studies met inclusion criteria. Narrative synthesis was conducted on the included studies. Five analytic themes emerged describing major stigma-related challenges: disclosure-related anxiety, medication adherence, feelings of abnormality, mental health issues and social exclusion. Disclosure-related anxiety and feelings of abnormality appeared to be largely confined to the experience of children and adolescents. Many of the themes centred around peer influence, highlighting the need to belong in youth. Results suggest that youth require tailored interventions targeting their age-specific challenges.