The Vaso-occlusive Crisis (VOC) is a very common manifestation of Sickle Cell Disease patients in India which is characterised by severe body, chest and joint pain. The patho-physiology of VOC is due to abnormal nitric oxide dependent regulation of vascular tone, adhesion of sickle cells (deoxygenated) to endothelium, platelet activation and inflammation. Therefore, nitric oxide inhalation may relieve such condition and also pain. The Nitric oxide inhalation therapy in sickle cell VOC cases is effective and also safe. It controls the acute pain significantly.