Aplastic anemia (AA) exemplifies immune-mediated bone marrow failure, presenting with pancytopenia, hypocellular marrow, and profound loss of hematopoietic stem-progenitor cells. Clinical success of antithymocyte globulin plus cyclosporine and allogeneic transplantation, the necessity for conditioning in syngeneic grafts, and dependence on long-term calcineurin inhibition implicate cytotoxic T cells and their cytokines (IFN-γ, TNF-α) as central pathogenic drivers. Single-cell and genomic studies reveal oligoclonal, patient-specific CD8+ expansions, Th17/Treg imbalance, and frequent clonal hematopoiesis that can either permit immune escape (paroxysmal nocturnal hemoglobinuria (PNH), human leukocyte antigens (HLA) loss) or herald myeloid evolution (RUNX1, splicing factor, ASXL1, monosomy 7). Short telomeres, inherited telomere repair and other germline mutations, plus inflammatory adipocyte-rich marrow, further promote genomic instability. Therapeutically, matched sibling transplantation remains curative for eligible patients; horse ATG/CsA with eltrombopag is the current first-line IST, while alternative donor, haploidentical and cord blood transplants, JAK inhibition, and TPO mimetics expand options for refractory disease.