Chronic inflammation ofmusculoskeletal structures is the most prominent disease manifestation of SpA. More specifically, the axial disease affects the spine, the sacroiliac joints and the hips. Peripheral disease includes peripheral arthritis, with a preference for asymmetrical inflammation ofjoints of the lower limbs and enthesitis, which is the presence of inflammation at the sites were ligaments and tendons attach to the bone. Additionally, SpA is often characterized by subclinical inflammation of the gut which partially resembles inflammatory bowel disease. Here, we will review the immunopathology of these different disease manifestations and relate them to clinical applications as well as emerging pathogenic concepts.