Ankylosing spondylitis (AS) is a common inflammatory arthritis in which genetic factors are the primary determinants of disease risk and severity. Substantial progress has been made in identifying genetic pathways involved in the disease, and in translating those discoveries to drug discovery programs. Recently discovered novel disease pathways include those involved in control of DNA methylation, bacterial sensing, and mucosal immunity. Additional pathways are likely to be identified as a higher proportion of the genetic risk of AS is determined.