<p>Haploidentical haematopoietic stem cell transplantation (haplo-HSCT) has transformed the management of haematological diseases by enabling the use of partially matched family donors, thereby markedly expanding donor availability. Advances in transplant platforms, including ex vivo TCRαβ⁺/CD19⁺ depletion and unmanipulated approaches such as the G-CSF/ anti-thymocyte globulin (ATG)-based Beijing protocol and post-transplant cyclophosphamide (PTCy)–based Baltimore protocol, have led to survival outcomes comparable to those of matched sibling donor transplantation. These strategies provide complementary advantages in graft-versus-host disease prevention, immune reconstitution, and logistical feasibility. Initially developed for common haematological malignancies, haplo-HSCT is increasingly applied to rare haematological, metabolic, and immunological disorders, for which suitable donors are often lacking and delayed treatment is associated with poor prognosis. Although individually uncommon, rare diseases collectively affect millions worldwide and are frequently genetic, progressive, and life-threatening, with limited curative options. While gene therapy represents a promising alternative, its widespread use is constrained by cost, accessibility, and long-term safety concerns. This review summarises current evidence supporting haplo-HSCT in rare diseases, compares outcomes across transplant platforms, and discusses disease-specific protocol adaptations, while highlighting future directions to improve safety and expand clinical applicability.</p>