Ankylosing spondylitis (AS) is a common rheumatic condition, highly heritable. Much of the genetic contribution to the disease lies in the major histocompatibility complex (MHC). The association with the allele group HLA-B*27 has been described worldwide for 30 years. On the other hand, genome wide scans have provided some interesting results showing that other MHC and non-MHC genes could be implicated either in disease susceptibility and phenotypic manifestations. Different hypothesis for disease pathophysiology have been investigated which contribute for a better understanding of the genetic basis of AS. This review aims to summarize the status of the knowledge in this exciting area. New data may, in a near future, change the screening of patients and generate new insights for the emergence of novel therapies.