Today there are at least four biological gases: oxygen (O2), nitric oxide (NO), carbon monoxide (CO), and hydrogen sulfide (H2S). Except for molecular oxygen, many of these gases were originally known for their detrimental physiological effects. However, the current consensus suggests that these gases play a role in signal transduction, modulating physiological function. The roles of these gases are complex as each is dependent on the rate of production, concentration, chemical reactivity, and availability of target proteins. Moreover, many of these gases share the same molecular targets, and thus are able to modify the responses to each other. This chapter discusses the chemistry of each of these gases, their biological production, potential interactions, and physiological consequences.