Granzyme A (GzmA) is an abundant serine protease in granules of cytotoxic lymphocytes that was traditionally thought (like granzyme B) to be involved in induction of cell death in target cells. However, an increasing body of evidence now suggests GzmA is a proinflammatory mediator, with levels elevated in a range of inflammatory and infectious diseases. We have recently shown that chikungunya virus arthritis is substantially ameliorated in GzmA-/- mice and that Serpinb6b, a specific inhibitor of mouse GzmA, is an effective treatment for chikungunya virus arthritis in wild-type mice (Wilson & Prow et al. 2017). CHIKV infected NHPs and CHIKV patients also show elevated levels of circulating GzmA; the latter recently confirmed by data from a Brazilian cohort. How GzmA promotes inflammation remains unclear, although data now points to cleavage of, and biased signalling by, Protease Activated Receptors (PARs), in particular PAR1 and PAR2, as being the key targets of GzmA's proinflammatory protease activity. Inhibitors of PAR1 (Vorapaxar) and PAR2 (I343) are able to inhibit both chikungunya virus and GzmA induced arthritis. The likely source of GzmA during chikunguya arthritis are cytotoxic CD4 cells and NK cells, with depletion of either of these cells ameliorating disease. We are currently looking at GzmA levels in dengue and Zika virus infections and developing strategies for new therapeutic interventions targeting GzmA’s activities.