Abstract Several lines of evidence point towards the central role of IL-23 as a crucial inflammatory mediator in the pathogenesis of SpA—a group of inflammatory arthritic diseases whose symptoms span the skin, gastrointestinal tract and joints. While therapeutic blockade of IL-23 proved successful in the treatment of IBD, psoriatic skin disease and peripheral SpA, it failed in patients suffering from SpA with predominantly axial involvement. Here we review state-of-the-art discoveries on IL-23 signalling pathways across target tissues involved in SpA. We discuss the discrepancies in resident IL-23–responding cells and their downstream activities across skin, gut and joint that shape the unique immunological landscape of SpA.