Dyskeratosis congenita (DC) is an inherited multisystem disorder that presents with characteristic mucocutaneous features and an inevitable bone marrow (BM) failure that is the main cause of mortality. The clinical presentation can vary widely in severity. X-linked, autosomal dominant (AD), and autosomal recessive (AR) inheritance forms are recognized. In the past two decades, the genetic and cellular bases of the DC syndrome have been elucidated, with an understanding that the mutations largely disrupt telomere maintenance. In this chapter, we review the pathobiology, clinical presentation, and management of DC, with a focus on the role of hematopoietic stem cell transplantation (HSCT).