Mast cells (MC), which are tissue-resident cells found widely distributed in the body, are derived from primitive hematopoietic cells. MC produce a variety of biologically active substances such as histamine, proteases, lipid derivatives and numerous cytokines and chemokines in response to immunologic or non-immunologic stimuli. Of interest, it has been reported that rodent MC can also be a source of nitric oxide (NO) derivatives, that they synthesize spontaneously, or only after activation, depending on their subtype. This synthesis appears to be under the control of the expression of the inducible isoform of the nitric oxide synthase (iNOS) and of the constitutive neuronal NOS (nNOS). MC might thus be able to influence the survival and functions of other types of NO-sensitive cells in close vicinity. Apart from being a source of NO, MC can also be the target for NO and its derivatives. Indeed, survival and reactivity of rodent MC is influenced by NO derivatives produced by MC themselves or by other cellular elements in close contact with the MC in tissues. By contrast, the existence of such mechanisms of cross-talk between MC and NO remains poorly documented in humans. If evidence are supplied in favor of such relationship, pharmacological modulation by agents acting at the level of the NO pathway might be of interest in order to regulate the functions of MC in immunologic, neoplastic, inflammatory and other conditions.