nitric oxide (NO), previously known as Endothelium-Derived Relaxing Factor (EDRF) is involved in a wide range of physiological and pathophysiological mechanisms. It is synthesized endogenously by the enzymes nitric oxide Synthase (NOS) in specialized tissues from its precursor L-arginine, yielding L-citrulline as a byproduct. It is released by a family of isoenzymes, viz., the endothelial (eNOS), neuronal (nNOS) and macrophage or inducible (iNOS). The three isoforms play distinct roles in the regulation of vascular tone. eNOS and nNOS are normal constituents of healthy cells, while iNOS is not usually expressed in vascular cells and its expression is seen mainly in conditions of inflammation or infection leading to overproduction of NO which acts as a killer molecule causing lethal oxidative injury. The excessive and prolonged NO generation mediated by iNOS has attracted attention. NO plays major roles in many systems, viz., cardiovascular, respiratory, renal, CNS, gastro-intestinal, immune, and so on. Hypofunctioning of NO is involved in hypertension, vasospastic diseases, impotency, gastroparesis and hypoxic pulmonary ventilation. On the other hand, hyperfunctioning is involved in diabetes, neurodegenerative diseases, epilepsy, septic shock and cerebral malaria. Phytochemicals capable of modulating NO production would exhibit potential pharmacological activities. The lecture sheds light upon the crucial role of NO in the pharmacological activities demonstrated by certain traditional herbs and phytochemicals isolated thereof. Examples of phytochemicals will be presented to illustrate their bioactivities controlled by their effect on NO production. Extracts from Hops (Humulus lupulus L.), as well as chalcones, isolated thereof, significantly inhibited NO production by suppressing the expression of iNOS. Diterpenes from Orthosiphon stamineus (used for a wide range of diseases) displayed significant inhibitory activity on NO production in LPS-activated macrophage-like J744.1 cells. The aqueous extract of red rice stimulated vascular endothelial cells to produce and/or release NO leading to endothelium-dependent relaxation. The acidic polysaccharide isolated from the ethanol-insoluble and water-soluble fraction of Panax ginseng exhibited an immunomodulating activity mediated by the production of NO and increased output of iNOS. Other selected examples will be presented in the lecture.