Nitric oxide (NO), synthesized from L-arginine by NO synthases, is a small, diffusible, highly reactive molecule with dichotomous regulatory roles under physiological and pathological con- ditions. Apoptosis plays an important role in the development of the organism but also under various pathological conditions. NO can exert both pro- and anti-apoptotic effects, depending on the conditions and cell type. Long-lasting production of NO acts as a proapoptotic modulator by activating caspase family proteases through the release of mitochondrial cytochrome c into the cytosol, upregulation of p53 expression, activation of JNK/SAPK, and altering the expression of apoptosis-associated proteins including Bcl-2 family proteins. However, low or physiological concentrations of NO prevent cells from apoptosis via expression of protective genes such as heat shock proteins, Bcl-2 as well as direct inhibition of the apoptotic caspase family proteases by S-nitrosylation of the cysteine thiol. Our current understanding of the mechanisms by which NO influences both pro- and antiapoptotic actions is discus- sed in this review.