Genetically inherited inborn errors of immunity result in impaired immune function and leave affected individuals exposed to increased risks of infection, inflammation, lymphoid malignancy and autoimmunity. Over 500 inborn errors of immunity are now described, affecting innate and adaptive immunity. Most are inherited in an autosomal recessive fashion, although some have X-linked recessive or autosomal dominant inheritance. For an increasing number of diseases, allogeneic haematopoietic cell transplantation (allo-HCT) is curative. The most severe of these diseases, severe combined immunodeficiencies, are considered as paediatric emergencies, and prompt diagnosis and supportive and curative treatment are required to achieve best outcomes. Recent advances in diagnostics and transplantation techniques are challenging our approach to treating many of these patients. This chapter will explore some of the issues that are currently topical.