Nitric oxide (NO) modulates the biological activity of proteins by direct interactions with their iron centres. It can also S-nitrosylate cysteines to form S-nitrosothiols. Such reactions affect the activity of membrane-bound, cytosolic and nuclear proteins including the NMDA receptor1, haemoglobin2 and transcription factors such as NF-κB3 and OxyR. NO is potentially toxic, inducing both apoptosis and necrosis. Here we show that NO-mediated S-nitrosylation of the cysteine-containing enzymes that mediate apoptosis (caspases and tissue-transglutaminase, tTG) regulates the balance between apoptosis and necrosis.