Introduction: The major histocompatibility complex, named the human leukocyte antigen system, is one of the most researched genetic systems. It is located on the short arm of the 6th. chromosome and it is made of antigens and alleles of class I, II and III. Being highly polymorphic, it is of exceptional importance in fields of transplantation medicine, population genetics and in diagnostics of various diseases. The main role of the HLA system is differentiation between organism's own cells and foreign cells and an adequate initiation of the immune response when in contact with foreign antigens. Autoimmune diseases develop when it comes to failure of the main role of immune system, that is, when an organism fails to recognise its own antigens and starts to react them as to foreign ones, attacking them. Numerous genes of the HLA system are tightly correlated with the development of autoimmune diseases like celiac disease, type I diabetes, thyroid diseases and a number of rheumatic diseases. Objective: To interpret the extreme importance of the HLA system in disease diagnostics and its correlation to various diseases including autoimmune diseases (rheumatoid arthritis, psoriatic arthritis, systemic sclerosis, celiac disease). Methods: To determine genes or antigens of the HLA system, tissue typing laboratories use both serological methods and methods of molecular biology. For determination of HLA antigens by serological method the microlymphocitotoxicity test is used (MLCT), while molecular methods for determining the alleles of HLA systems are PCR – SSP (Polymerase Chain Reaction with Specific Sequence Primers) and PCR – SSO (Polymerase Chain Reaction with Specific Sequence Oligonucleotide). Conclusion: The determination of antigens and alleles of the HLA system in patients with rheumatoid diseases is of exceptional value both in diagnostics and patient's treatment. With the development of molecular biology methods, new findings about the HLA system and its correlation to diseases arise daily.