Nitric oxide has emerged as one of the most important and diverse players in physiology. This small diatomic radical stunned researchers because of its existence and unique biological properties in human physiology. Over the last two decades it was found that NO often has fickle behavior in pathophysiological mechanisms. Where benefiting the host in one case yet inducing and augmenting injury in another. This has lead to confusion in is NO good or bad? Much of the answers to this dichotomy lies in the chemistry of NO and its related nitrogen oxide species. To help understand the complex chemistry with perspective to biology, a discussion on the chemical biology of NO is useful. The chemical biology defines the relevant chemical reaction of NO and nitrogen monoxide in the context of the biological conditions. We discuss in this article the chemistry of nitrogen oxide with different types of biological motifs. Reaction of NO with metal complexes and radicals require low concentration, where formation of reactive nitrogen oxide species require considerably higher amounts and generally are isolated to specific microenvironments in vivo. Though many reactive nitrogen oxide species are formed from chemical reactions with NO, there are several which appear to not require NO to be present, HNO and NO(2). These two species have unique physiological effects and represent additional complexity to this biological picture. From this discussion, a picture can be formed concerning the possible chemical dynamics, which can be plausible in different biological mechanisms.