<p>Brain disease is ultimately a disease of its constituent cells, and single-cell genomics has recently begun to illuminate the cellular pathologies underlying human brain disorders. In this review, we synthesize the key biological insights from recent single-cell studies of post-mortem human brain tissue across a range of neurological and psychiatric conditions. Organized by major central nervous system cell type, we detail the depletion of vulnerable cellular populations, the emergence of disease-associated states, the dysregulation of gene expression programs, and the interplay between these changes and genetic risk factors. Collectively, these studies mark a turning point in brain disease research, providing the first comprehensive maps of how neurological and psychiatric disorders manifest across the cellular landscape of the human brain.</p>