Non-steroidal anti-inflammatory drugs are among the most commonly used drugs. Despite efforts to produce non-steroidal anti-inflammatory drugs that do not cause gastrointestinal ulceration and bleeding, these adverse effects remain major limitations to their use. In recent years, physiological roles of hydrogen sulfide (H2S) have been recognized, and there is emerging evidence that this endogenous gaseous substance can modulate inflammatory processes. Indeed, H2S donors have been shown to reduce edema formation and leukocyte adherence to the vascular endothelium, and to inhibit pro-inflammatory cytokine synthesis. Moreover, H2S donors can increase the resistance of the gastric mucosa to injury and accelerate repair. Taken together, these observations and others suggest that anti-inflammatory drugs that are modified to release H2S will exhibit improved efficacy and reduced toxicity. Such compounds have now been synthesized and shown to be markedly improved in many respects over the parent anti-inflammatory drugs.