This review of ankylosing spondylitis (AS) mechanisms is an update on current AS theories and suggestions for continued research. A literature search identified two leading hypotheses on possible mechanisms–the arthritogenic peptide hypothesis and the misfolding hypothesis– as well as three additional factors that may influence the progression of the disease. These studies have raised as many questions as they answered, and there is often a significant time gap between studies on the same topic due to the difficulties and costs involved. Continued research on this prevalent and debilitating disease remains imperative, especially in light of recent breakthroughs in immunotherapy such as CAR T cell therapy. This review explores the two major mechanistic hypotheses, then discusses emerging genetic and immunologic findings, and the potential of CAR T cell therapy.