Henry Jay Forman, Jon Fukuto and Martine Torres Research is to see what everybody else has seen and to think what body else has thought. -- Albert Szent-Gyorgyi Several years ago, one of us put together a book that dealt with various aspects of oxidative stress and introduced the concept of signal transduction by oxidants. Since then, the interest in the mechanisms by which reactive oxygen and nitrogen species (ROS/RNS) can modulate the cell's response has tremendously grown, paralleling the intense efforts towards identifying new signaling pathways in which phosphorylation/dephosphorylation events take center stage. Evidence is w mounting that production of these species by the cells is required for their function from growth to apoptosis and numerous signaling pathways have been identified where the participation of ROS and RNS is apparent (see Chapters 11-14, 16 and 18). Thus, the field is more limited to the group of free radical aficionados who have pioneered this area of research but has w gone mainstream. While it is satisfactory for those of us who have been working on this topic for a long time, it has the risk of becoming the fashionable motto where those molecules, still mysterious to some, become responsible for everything and anything.