Ammonia (NH₃) as a free gaseous molecule is produced in mammalian cells via an array of metabolic pathways. Its importance as a metabolic product and a fundamental element in the make-up of macromolecules has been recognized, but its participation and contribution to cellular signaling processes have been largely overlooked. This chapter discusses the endogenous generation, metabolism, and biological functions of gaseous ammonia under physiological and pathological conditions, such as hyperammonemia and hepatic encephalopathy. The role of ammonia as a gasotransmitter is specially examined, considering its unique and different properties from those of other gasotransmitters.