OBJECTIVES To elucidate the relationship between the course of bipolar disorder (BD) and structural brain changes across the life span, we conducted a systematic review of longitudinal imaging studies in adolescent and adult BD-patients. METHODS Eleven studies with 329 BD-patients and 277 controls met our PICOS-criteria (participants, intervention, comparison, outcome, study design): BD-diagnosis based on DSM criteria, natural course of disease, comparison of grey matter changes in BD-individuals over ≥1 year interval between scans. RESULTS The selected studies yielded heterogeneous findings, partly due to varying patient characteristics, data acquisition and statistical models. Mood episodes were associated with greater grey matter loss in frontal brain regions over time. Brain volume decreased or remained stable in paediatric patients, whereas it increased in healthy children and adolescents. Adult BD-patients showed increased cortical thinning and brain structural decline. In particular, disease onset in adolescence was associated with amygdala volume reduction, which was not reported in adult BD. CONCLUSIONS The evidence collected suggests that the progression of BD impairs paediatric brain development and accelerates structural brain decline across the lifespan. Age-specific changes in amygdala volume in paediatric BD suggests that reduced amygdala volume is a correlate of early onset BD. Clarifying the role of BD in brain-development across the life span promises a deeper understanding of the progression of BD patients through different developmental episodes.