Spondyloarthritis (SpA) is characterized by inflammation and new bone formation in the spine and entheses. The disease is the result of a complex interplay among susceptibility genes, microbial triggers, inflammation of bone marrow, and the enthesial structures and new bone formation. This article gives a conceptual overview of the major insights into the pathophysiology of SpA and discusses the main genes associated with SpA, as well as other factors that are involved in the onset of inflammation. It also addresses the nature of inflammation in SpA and the mechanisms of ankylosis.