Endogenous and exogenous nitric oxide (NO) possesses antiparasitic effects on both Protozoa and Metazoa. However, NO production requires a tight control to limit cytotoxic damage to the host's own cells. The best known parasitic macromolecular targets for NO(-donors) are cysteine proteases, which are relevant in several aspects of the parasite life cycle and parasite-host relationships, and appear as promising targets for anti-parasitic chemotherapy.