Telomeres are protective DNA–protein complexes at the ends of chromosomes that maintain genomic integrity. Telomere shortening occurs with cell division and is counteracted by telomerase and shelterin complex components. Mutations in genes involved in telomere maintenance lead to telomere biology disorders (TBDs), a spectrum of inherited syndromes, including dyskeratosis congenita (DC), Hoyeraal–Hreidarsson syndrome (HHS), Revesz syndrome, and Coats plus. TBDs are associated with multiorgan manifestations, such as bone marrow failure, pulmonary fibrosis, liver disease, immunodeficiency, and increased cancer risk. Diagnosis relies on telomere length testing (e.g., flow-FISH) and genetic analysis, though somatic reversion and unknown variants complicate diagnosis. Management includes surveillance, supportive care, and organ- or disease-specific therapies. Hematopoietic stem cell transplantation (HSCT) and androgen therapy offer benefits in select patients, while solid organ transplantation may be required for end organ failure. Emerging therapies targeting telomerase restoration are under investigation. Understanding telomere biology is essential for diagnosing and managing this complex and evolving group of disorders.