N p b i t e p b a m a f d p i he field of plastic surgery has been dealing with the olecular mechanisms affecting flap survival since the dvent of molecular biology. The characterization of he milieu of tissue factor and cell-signaling molecules hat contribute to flap survival or necrosis continues to eceive interest from investigators. In recent years, nitric xide (NO) has received attention as a prospective canidate for manipulation to prevent or counteract the etrimental effects of tissue trauma and ischemia that he flap experiences during these procedures. NO is an mportant biologic signaling molecule and has been roved to be involved in signaling at the neuronal synpse, to function as a host defense effector in the imune system, to be pathologically cytotoxic as a free adical, and to regulate basal vessel tone in the cardioascular system. As such, an overall assessment of NO unction in the skin flap requires attention to its many ffects to properly characterize its influence on flap surival. The field of NO research is continually expanding, nd a discussion of all of its known physiologic effects in he context of tissue ischemia and flap survival is a subtantial task. NO plays a broad role in ischemic injury, nd has been studied extensively in relation to bowel, iver, myocardium, lungs, and CNS, and is often menioned in the context of transplantation surgery. The resent discussion is limited to the most pertinent and ell-developed areas of the field and their relation to laps. Because many tissues react similarly to ischemic nsult, some elements of the discussion concerning vasular effects, free radicals, and inflammation are appliable to injuries of various tissues throughout the body. Since the characterization in 1987 of endotheliumerived relaxing factor as NO, a significant volume of esearch has been published investigating its role in the ascular endothelium and its application to survival of urgical flaps. Ischemia-reperfusion injury has been ad-