The social and economic impact of chronic inflammatory diseases, such as arthritis, explains the growing interest of the research in this field. The antioxidant and anti-inflammatory properties of the endogenous gasotransmitter hydrogen sulfide (H 2 S) were recently demonstrated in the context of different inflammatory diseases. In particular, H 2 S is able to suppress the production of pro-inflammatory mediations by lymphocytes and innate immunity cells. Considering these biological effects of H 2 S, a potential role in the treatment of inflammatory arthritis, such as rheumatoid arthritis (RA), can be postulated. However, despite the growing interest in H 2 S, more evidence is needed to understand the pathophysiology and the potential of H 2 S as a therapeutic agent. Within this review, we provide an overview on H 2 S biological effects, on its role in immune-mediated inflammatory diseases, on H 2 S releasing drugs, and on systems of tissue repair and regeneration that are currently under investigation for potential therapeutic applications in arthritic diseases.