Nitric oxide (NO) has been found to play an important role as a signal molecule in many parts of the organism as well as a cytotoxic effector molecule of the nonspecific immune response. It appears paradoxical that NO on one side acts as a physiological intercellular messenger and on the other side may display cytotoxic activity in vivo. To make things even more complicated, cytoprotective properties of NO are also described. We here review the current understanding of cytotoxic versus cytoprotective effects of NO in mammalian cells and try to highlight the janus-faced properties of this important small molecule.