Hemophilia B is a severe X-linked recessive disorder caused by mutations in the F9 gene, which encodes blood coagulation factor IX (FIX). This review article examines the main types of mutations and their impact on the structure and function of FIX, as well as the correlation between genetic defects and the clinical manifestations of the disease. The existing approaches to replacement therapy, their efficacy, and potential complications (such as the development of inhibitory antibodies) are discussed. Additionally, the possibilities of using gene therapy for the treatment of hemophilia B are explored, as gene therapy is now emerging as a key treatment method capable of restoring long-term FIX production. Specifically, for disease forms caused by splicing defects, approaches such as antisense oligonucleotides (ASOs) and the CRISPR/Cas9 system are proposed, which can correct specific mutations and improve treatment efficacy.