Systemic lupus erythematosus (SLE) is a chronic autoimmune rheumatic condition, affecting multiple organ systems, characterised by an unpredictable course, with periods of high disease activity requiring intense immunosuppressive treatment, potentially leading to damage accumulation over many years. SLE begins in childhood and adolescence in up to 15–20% of cases. Clinicians should consider this possible diagnosis in adolescents and young adults (AYA) presenting with multi-system manifestations associated with distinct serological markers, or new onset nephritis. Care for the AYA with childhood-onset SLE (cSLE) requires a multidisciplinary approach, monitoring for impact of disease and therapy on AYA physical and cognitive development, as well as organ-specific function, aiming to minimise damage accrual over time and their overall co-morbidity risk.