Bipolar disorder (BD) akin to other psychiatric conditions still lacks a specific neuropathologic substrate or a well-defined neuropathological diagnostic criterion. The quest for reliable neural biomarkers of BD is further complicated by the lack of specificity in findings and the prevalence of underpowered studies. Substantial clinical and methodological heterogeneity across experiments poses an additional challenge in pinpointing consistent neural mechanisms underlying BD. In summary, studies reveal structural changes in various brain regions in BD patients. The concurrent presence of macroscopic and microscopic changes in several brain regions suggests interconnected abnormalities. At the molecular level, reduction in brain cell numbers may intertwine with heightened inflammation and disruptions in protein degradation pathways, potentially culminating in cell death. This proposed mechanism offers valuable insights into the trajectory of BD, the occurrence of relapses, and the heightened difficulty of post-episodes recovery. No structural brain differences were detected between BD subtypes. Collaborative efforts focusing on the analyses of the same brain cells, molecular alterations, and brain regions across different cohorts will be crucial to provide more robust findings and insights into the physiopathology of BD.