Nitric oxide (NO), which is synthesized by the enzyme NO synthase (NOS), is a versatile endogenous molecule with multiple biological effects on many tissues and organs. In dental pulp tissue, NO has been found to play multifaceted roles in regulating physiological activities, inflammation processes, and tissue repair events, such as cell proliferation, neuronal degeneration, angiogenesis, and odontoblastic differentiation. However, there is a deficiency of detailed discussion on the NO-mediated interactions between inflammation and reparative/ regenerative responses in wounded dental pulp tissue, which is a central determinant of ultimate clinical outcomes. Thus, the purpose of this review is to outline the current molecular understanding on the roles of Janusfaced molecule NO in dental pulp physiology, inflammation, and reparative activities. Based on this knowledge, advanced physicochemical techniques designed to manipulate the therapeutic potential of NOS and NO production in endodontic regeneration procedures are further discussed.